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Current Medicinal Chemistry, XXXX, XX, XX-XX 1
REVIEW ARTICLE
0929-8673/XX $65.00+.00 © XXXX Bentham Science Publishers
Biogenic Carbon Quantum Dots: Synthesis and Applications
Ankita Deb1 and Devasish Chowdhury1,*
1Material Nanochemistry Laboratory, Physical Sciences Division, Institute of Advanced Study in Science and
Technology, Paschim Boragaon, Garchuk, Guwahati-781035, India
Abstract: The new class of nanomaterials termed carbon dots: a quasi-spherical nanopar-
ticle having a size less than 10 nm, possesses some unique characteristics like good aque-
ous solubility, colloidal stability, resistance to photobleaching, and fluorescence tunabil-
ity, resulting in the unfolding of their various properties and their usage in different appli-
cations. Materials that are naturally derived or produced by living organisms are termed
‘biogenic’. Over the past few years, there has been a gradual increase in the use of natural-
ly derived materials in synthesizing carbon dots. Green precursors or biogenic materials
are of low cost, readily available, renewable, and environmentally benign. Most im-
portantly, they provide essential benefits not found in synthesized carbon dots. This re-
view focuses on the use of biogenic materials for the synthesis of biogenic carbon dots
developed in the past five years. It also briefly explains different synthetic protocols used,
along with some significant findings. Thereafter, an overview of the use of biogenic car-
bon dots (BCDs) in different applications like chemo and biosensors, drug delivery, bi-
oimaging, catalysis and energy applications, etc., is discussed. Thus biogenic carbon dots
are future sustainable materials that are now fast replacing conventional carbon quantum
prepared from other sources.
A R T I C L E H I S T O R Y
Received: January 23, 2023
Revised: April 26, 2023
Accepted: May 18, 2023
DOI:
10.2174/0929867330666230608105201
Keywords: Biogenic, carbon, quantum dots, nanomaterials, zero-dimensional, electron.
1. INTRODUCTION
The unprecedented discovery of a zero-dimensional
nanomaterial back in 2004 has enthralled the scientific
community to explore the material. This new class of
nanomaterials termed carbon dots is a quasi-spherical
nanoparticle having a size of less than 10 nm, which
was obtained during the separation and purification of
single-walled carbon nanotubes [1]. Carbon dots (CDs)
possess some unique characteristics like good aqueous
solubility, colloidal stability, resistant to photobleach-
ing, and fluorescence tunability, resulting in the unfold-
ing of their various properties and their usage in differ-
ent applications [2]. In fact, the utilization of carbon
dots can be roughly categorized based on their proper-
ties. The electron donor-acceptor property of carbon
dots entrusts them to be used in optronics and catalysis
[3]. On the other hand, the pre-requisite biological
*Address correspondence to this author at the Material Nanochem-
istry Laboratory, Physical Sciences Division, Institute of Advanced
Study in Science and Technology, Paschim Boragaon, Garchuk,
Guwahati-781035, India; E-mail: devasish@iasst.gov.in
properties like chemical inertness, low cytotoxicity,and
good biocompatibility enable the CDs to be used in
biomedical applications [4]. Therefore, CDs have out-
grown as a potential candidate amongst other nano-
materials.
Apart from the nature and properties of carbon dots,
another aspect required to consider is the precursor,
which is the raw material used in preparing the carbon
dots. These carbon dots can be divided based on the
carbon sources used: biogenic carbon dots and carbon
dots prepared from other sources. The former refers to
materials that are naturally derived or produced by liv-
ing organisms, and hence the term 'biogenic' is used,
whereas the latter involves the use of carbon soot, am-
monium citrate, graphite, ethylenediamine, fullerene-
C60, boronic acid [5-10]. Over the past few years, there
has been a gradual increase in the use of naturally de-
rived materials in synthesizing carbon dots. Green pre-
cursors or biogenic materials are low-cost, easy availa-
bility, renewable, and environmentally benign.
2 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
Most importantly, they provide some essential bene-
fits, which otherwise are not possible in carbon dots
synthesized from other sources. First, biogenic carbon
dots (BCDs) have the ability to convert low-value bio-
mass or agricultural or industrial waste into valuable
materials, reducing environmental waste [11]. Second-
ly, carbon dots synthesized from other sources suffer
from low quantum yield (<10%), and in order to en-
hance it, an additional step of doping heteroatom(s) is
required during synthesis. However, the inherent pres-
ence of heteroatoms such as nitrogen and/or sulfur in
some natural products leads to high-quality BCDs with
improved optical properties and quantum yield, elimi-
nating the extra step of heteroatom doping and easy-to-
synthesize protocols [12]. Many reports documented
nitrogen-doped BCDs, as a perfect choice for biomedi-
cal applications [13]. Moreover, the different phyto-
constituents and bioactive components present in the
biogenic materials provide exposure to various func-
tional groups and adaptability to dopants and solvents,
making them potential materials to synthesize BCDs
[14]. In fact, the different functionalities enable the
formation of different surface states on the BCDs.
Liu et al. was the pioneer who successfully synthesized
carbon dots using grass as the precursor [15]. That ca-
talysis the trend to use biogenic materials for the syn-
thesis of carbon dots.
Herein, this review will focus on the use of biogenic
materials for CDs synthesis in the past five years by
providing a brief idea of the different synthetic proto-
cols used along with some significant findings. There-
after, we overview the use of BCDs in sensing applica-
tions to detect biomolecules and important molecules
in the biological system (Fig. 1).
Fig. (1). Schematic representation depicting the various pre-
cursors used in the synthesis of biogenic carbon dots and
their applications. (A higher resolution/colour version of this
figure is available in the electronic copy of the article).
2. METHODS OF SYNTHESIS
Two primary approaches to the synthesis of carbon
dots are top-down and bottom-up. As the name sug-
gests, the top-down method involves breaking down
large entities into smaller nanoscale entities by differ-
ent physical and chemical methods like high-energy
ball milling, laser ablation, arc discharge, and electro-
chemical techniques [16]. S Some carbon precursors
like graphite, candle soot were used in preparing car-
bon dots by these methods [5, 17]. On the other hand,
the bottom-up strategy involves aggregating small mol-
ecules/molecular moieties via different carbonization
techniques like hydrothermal, microwave irradiation,
pyrolysis, and chemical oxidation [16]. BCDs are gen-
erally prepared using the bottom-up approach as it of-
fers several advantages like it is comparatively much
simpler, easier, and faster [18]. It has adequate control
over the size of the product and the route. The process
is also considered green and cost-effective.
The following section will focus on the CDs derived
from various biogenic sources discussing their mode of
synthesis.
3. DIFFERENT TYPES OF CARBON DOTS DE-
RIVED FROM BIOGENIC SOURCES
Years before the first synthesis of carbon dots from
naturally derived precursors, the synthesis of carbon dots
was limited to carbonaceous precursors, and the carbon
dot obtained was of low quantum yield and poor solubil-
ity. The idea to explore green or biogenic sources to
form BCDs has created a paradigm shift as the problems
could be addressed. The choice of the method used to
synthesize BCDs was optimized according to the quan-
tum yield achieved. Nevertheless, the quantum yield and
solubility could be enhanced by some chemical treat-
ment or by adding surface passivating agents during syn-
thesis. Biogenic sources include fruits, vegetables, other
plant-derived parts, human derivatives, microorganisms,
and biomass wastes. This section encompasses the use
of various biogenic sources to synthesize BCDs by cate-
gorizing the sources for ease of understanding.
3.1. Carbon Dots Derived from Fruits
Fruit comprises phytochemicals, fibers, and vita-
mins which act as the main carbon content for carbon
dot formation. The preparation involves either taking
the raw fruit or its juice to disperse in a suitable sol-
vent. Following the use of grass as a carbon dot-
forming source, to date a large number of fruits were
being utilized to synthesize BCDs. To begin with, high-
ly fluorescent BCDs were prepared from coconut water
dispersed in ethanol via microwave-assisted hydro-
CHEMO-&(
BIO-
SENSORS
DRUG(
DELIVERY
BIO-
IMAGING
CDs
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 3
thermal method at different temperatures ranging from
130ºC to 180ºC for 1 minute [19]. The particle size var-
ied between 1-6 nm on changing temperature. It was
shown that at high temperatures, graphitic defect sites
were introduced in the carbon core. The carbon dot
suspension was even found to be stable for 11 months
without any agglomeration or alteration in PL proper-
ties. Similarly, papaya was used as a raw material to
synthesize N-doped CDs by hydrothermal method with
no further modification [20]. The CDs were prepared in
water and ethanol, both showing excellent QY of
~18%. An important observation in this study was that
the average particle size of water-dispersed CDs was
3.4 nm and that of ethanol-dispersed CDs was 10.8 nm.
Wang et al. explained the presence of saccharides and
other water-soluble molecules in aqueous medium,
leading to the formation of small-sized CDs. On the
other hand, Liao and his co-workers reported the syn-
thesis of water-soluble N-doped CDs from peach gum
polysaccharide (PGP) and ethylenediamine via one-pot
hydrothermal carbonization [21]. The resulting CDs
had an enhanced QY of 28.46% compared to that of
undoped CDs (5.3%). The presence of carboxylic acid
functional groups (derived from uronic acid) helped in
the successful implementation of nitrogen in the CDs
during the hydrothermal process. Similarly, following
the same synthesis protocol, N-doped CDs were syn-
thesized from dragon fruit (Hylocereus undatus) extract
and aqueous ammonia [22]. The phytochemical study
of dragon fruit showed the presence of triterpenoids,
flavonoids, and vitamin C and therefore acted as a suit-
able carbon precursor. Arul and his co-workers used
kiwi fruit (Actinidia deliciosa) extract as the green car-
bon source to synthesize CDs by hydrothermal carbon-
ization [23]. They also used aqueous ammonia as the
nitrogen doping agent to enhance the fluorescent prop-
erty. The major phytochemicals like-tocopherols, caf-
feic acid, and quercetin along with vitamins acted as
potential candidates for carbon dot formation. Next,
biogenic CDs were prepared from pulp-free lemon
juice with ethanol by hydrothermal treatment [24]. The
temperature was set at 120ºC and took only 3 h to
complete, a much lesser time than that of the usual re-
ported hydrothermal method. This process yielded CDs
of uniform morphology, crystalline structure, and with
a good QY of 16.7%. The presence of sugars along
with organic acids like citric acid, and ascorbic acid in
the lemon juice contributed to the production of good
quality CDs. Similarly, BCDs were synthesized from
grapes, apple, mango, and watermelon juices by hydro-
thermal treatment, all of which showed a slight crystal-
line character surrounded with amorphous carbon do-
mains [25, 26]. In another work, both nitrogen and sul-
phur-doped BCDs were prepared by mixing lemon
juice with onion juice (as S-dopant) and ammonium
hydroxide (as N-dopant) via microwave irradiation
technique [27]. The presence of different types of func-
tional groups like hydroxyl, amino, and sulfite on the
CDs induced by the dopants conferred a high QY of
23.6% and excellent water solubility. Star fruit (Aver-
rhoa carambola) contains several phytoconstituents
ranging from sugars, polyphenols, and organic acids
and was chosen as a carbon precursor for the produc-
tion of CDs [28]. The reaction was carried out hydro-
thermally, however, to improve the optical properties,
Zulfajri et al. used an amino acid, and L-arginine as the
nitrogen dopant. The BCDs obtained has a good QY of
12.35%. The improved PL property of the BCDs was
attributed to the formation of good emissive states due
to the presence of N-rich groups. Another interesting
work involves the fabrication of multicolor emissive
CDs from muskmelon fruit [29]. Blue, green, and yel-
low color CDs were obtained via acid oxidation at dif-
ferent experimental conditions having good QY of 7%,
26.9%, and 14.3%, respectively. The presence of bioac-
tive components like folic acid, pro-vitamin A, vitamin
C, flavonoids, and cucurbitacin together plays an im-
portant role in generating BCDs. Similarly, realizing
the presence of high phenolic and polyphenolic con-
tents along with the high rate of production, kiwi, pear,
and avocado were also used as carbon sources for syn-
thesizing CDs by one-pot hydrothermal method [30].
Other biogenic sources from fruits include amla, cherry
plum, Chiku, corn, and pineapple which are reported to
serve as precursors for synthesizing BCDs [31-35].
Table 1 lists the different fruits used in preparing
BCDs. However, the list is not exhaustive.
3.2. Carbon Dots Derived from Vegetables
The extensive use of fruits has also prompted re-
searchers to explore vegetables for carbon dot synthe-
sis. Liu et al. developed fluorescent BCDs from Rose-
heart radish via one-pot hydrothermal treatment at
180ºC for 3 h and obtained a satisfactory QY of 13.6%
[36]. Rose-heart radish contains anthocyanins, a water-
soluble pigment along with carbohydrates and proteins,
and therefore, could serve both as a carbon precursor
for the production of nitrogen-doped CDs and for easy
functionalization post-synthesis. The as-prepared
BCDs exhibited high stability as there was no signifi-
cant PL intensity even after irradiation by a 500 W Xe
lamp for 3 h. Shen et al. used sweet potato to produce
BCDs through a hydrothermal method with a QY of
8.6% [37]. Cruciferous vegetables such as broccoli,
cauliflower, and romanesco contain high amounts of
glucosinolates (S-linked glucosides) and can be
4 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
Table 1. BCDs prepared from fruits along with different synthetic routes applied.
Precursors
Method
Solvent
Additive
References
Coconut water
Microwave-assisted
hydrothermal
Ethanol
-
[19]
Papaya
Hydrothermal
Water and ethanol
-
[20]
Peach gum polysaccharide
Hydrothermal
Aq. ethanol
Ethylenediamine
[21]
Dragon fruit
Hydrothermal
Aq. ammonia
-
[22]
Kiwi fruit
Hydrothermal
Aq. ammonia
-
[23]
Pulp-free lemon
Hydrothermal
Ethanol
-
[24]
Grapes, apple, mango, watermelon
Hydrothermal
Water
-
[25, 26]
Onion juice
Microwave
Water
Ammonium hydroxide
[27]
Star fruit
Hydrothermal
Water
L-Arginine
[28]
Muskmelon
Acid-oxidation
Water
-
[29]
Kiwi, pear, and avocado
Hydrothermal
Water
-
[30]
Amla
Hydrothermal
Water
Aq. Ammonia
[31]
Cherry plum
Hydrothermal
Water
-
[32]
Chiku (Manilkara zapota)
Acid-oxidation
Water
-
[33]
Corn
Hydrothermal
Water
-
[34]
Pineapple
Acid-oxidation
Water
-
[35]
exploited to promote S-doping to generate high-quality
fluorescent BCDs. Romero et al. used broccoli to pro-
duce highly fluorescent N, S co-doped carbon dots by
photochemical oxidation of carbohydrates extracted
from broccoli [38]. An excellent QY of 22% was ob-
tained. The heteroatom doping allowed more active
sites in the BCDs resulting in the enhancement of PL
properties. Here, N is derived from the vita-
mins/proteins present in the vegetable. Following this,
S-doped CDs were synthesized using pesticide-free
cauliflower juice by one-step hydrothermal carboniza-
tion [39]. The prepared CDs showed an excellent QY
of 43%. The presence of heteroatom and self-surface
passivation that occurred during synthesis could result
in such a high value of QY. Syntheses of N, S co-
doped CDs are also reported by Hu and his group from
onion and water chestnut in a simple autoclave system
at 180ºC for 4 h having QY of 12% [40]. Onion con-
tains thiol compounds whereas water chestnut contains
nitrogenous compounds and therefore acts as sul-
phur(S) source and nitrogen (N) source, respectively,
for fabricating the biogenic CDs. Lia et al. used toma-
toes to produce water-soluble BCDs hydrothermally at
180ºC and 6 h as the optimized reaction condition, giv-
ing QY of ~10% [41]. Another study by Konwar et al.
demonstrated the use of highly conjugated carotenoids
extracted from carrots as a biogenic source for CDs
[42]. Here the extracted carotenoid itself showed an
emission peak, however, when subjected to microwave
treatment to form CDs gave rise to a dual emission
peak with QY of 4% only. With the addition of eth-
ylene glycol, there is a prominent rise in QY to 22.5%
which clearly implied the role of oxygen-containing
functional groups as a passivating agent in reducing the
non-radiative recombination. CDs prepared from spring
onion (scallion leaves) hydrothermally are intrinsically
N- and S-co-doped giving QY of 23% [43]. Table 2
displays the overall vegetables that have been used for
preparing BCDs.
3.3. Carbon Dots Derived from Fruit and Vegetable
Peels
A large number of inedible fruit peels, which are be-
ing discarded, consist mainly of fibers and proteins that
can serve as excellent carbon precursors for the synthe-
sis of BCDs. There are several reports of the use of
fruit peels to generate BCDs, among which lemon and
orange peels are being extensively used. Tyagi et al.
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 5
Table 2. BCDs prepared from vegetables along with different synthetic routes applied.
Precursors
Method
Solvent
Additive
References
Rose-heart radish
Hydrothermal
Water
-
[36]
Sweet potato
Hydrothermal
Water
-
[37]
Broccoli
Photochemical oxidation
Water
-
[38]
Cauliflower
Hydrothermal
Water
-
[39]
Onion and water chestnut
Hydrothermal
Water
-
[40]
Tomato
Hydrothermal
Water
-
[41]
Carrots
Microwave
Ethanol
-
[42]
Spring onion
Hydrothermal
Water
-
[43]
reported a hydrothermal route to synthesis BCDs from
the lemon peel with QY of 14% [44], whereas Chat-
zimitakos et al. adopted a pyrolysis route and calculat-
ed to find a slightly improved QY of 15.5% [45]. Nota-
bly, the BCDs obtained by pyrolysis showed dual
emission peaks in the blue and violet regions. There-
fore, the mode of synthesis modulates the carbon dot
formation, which, in turn, influences the emission be-
haviour. Similarly, orange peels were also utilized as
carbon sources to generate BCDs via different synthet-
ic techniques; for example, Chatzimitakos et al. syn-
thesized by pyrolysis method [45], Gudimella et al.
used sand bath assisted strategy [46] and Wang et al.
used one step hydrothermal route [47]. An interesting
finding documented by Wang and his group was that
the QYs of the generated CDs are proportional to the
amounts of volatile oils extracted from a variety of or-
ange peels. From this finding, it was concluded that the
volatile oils might be a component of the peels which
was reflected in the fluorescent properties of the CDs.
BCDs were also prepared from pineapple peel via hy-
drothermal treatment with an excellent QY of 42%
[48]. Pineapple peels possess a cellulosic component
which serves as a rich carbon source for synthesis.
Atchudan et al. reported the use of banana peel to pro-
duce water-soluble nitrogen-doped CDs hydrothermal-
ly with a high QY of 23%, where aqueous ammonia
was used as an N-dopant [49]. Recently, BCDs from
the extracts of pomegranate and watermelon peels were
synthesized via the microwave irradiation method [50].
The duration of the reaction was 2 minutes. The BCDs
showed antimicrobial activity against Escherichia coli,
Staphylococcus aureus, Fusarium oxysporum, Bacillus
subtilis, etc. On the other hand, Jiao et al. proposed an
eco-friendly approach by combining pyrolyzation with
oxygenolysis to produce CDs from mango peel without
any post-treatment yielding QY of ~8% [51]. Other
sources include peels of lychee, sweet potato, durian
shell that have been used as carbon precursors for pre-
paring BCDs [52-54]. Table 3 provides a list of the var-
ious use of fruits and vegetable peels as choice of pre-
cursors.
3.4. Carbon Dots Derived from Seeds and Spices
Date kernels which are usually discarded, are a rich
source of carbohydrates, proteins, and fats, and there-
fore, can serve as a good carbon source for N-doped
CDs. Amin et al. prepared water-soluble N-CDs by
one-pot hydrothermal synthesis, resulting in QY 12.5%
[55]. Similarly, other N-CDs were also derived from
mustard seeds and jackfruit seeds with QY 4.6% and
17.9%, respectively [56, 57]. The CDs from mustard
seeds were obtained hydrothermally at 180ºC for 4 h,
whereas CDs from jackfruit seeds were by microwave-
assisted method at 600 W for 1 min 30 sec. In the latter
case, a mild acid, o-phosphoric acid was added to in-
crease the polarity of the mixture so that the maximum
microwave radiation could be absorbed by the mixture.
The BCDs synthesized from groundnut by hydrother-
mal treatment required a high temperature of 250ºC for
6 h [58] with QY 7.8%. BCDs were also produced
from kiwi seeds, black sesame, and white sesame seeds
via pyrolysis at 350ºC for 10 h [59].
Common spices such as black and white pepper, red
chilli, turmeric, and cinnamon are known for their me-
dicinal properties due to the presence of bioactive
components like piperine, capsaicin, curcumin, and
cinnamaldehyde respectively. These spices, therefore,
could act as a potential carbon source for BCD produc-
tion. Vasimalai et al. adopted the green hydrothermal
method to synthesize water-soluble fluorescent BCDs
from cinnamon, turmeric, red chilli, and black pepper
at 200ºC for 12 h with excellent QY of 35.7%, 38.3%,
26.8%, 43.6% respectively [60]. Besides, all of them
had high values of negative zeta potential, ensuring
high colloidal stability of the spice-based CDs in
6 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
Table 3. BCDs prepared from fruit and vegetable peels along with different synthetic routes applied.
Precursors
Method
Solvent
Additive
References
Lemon peel
Hydrothermal/ pyrolysis
Water
-
[44, 45]
Orange peel
Pyrolysis/sand bath assisted
strategy/ hydrothermal
Water
-
[45-47]
Pineapple peel
Hydrothermal
Ethanol
-
[48]
Banana peel
Hydrothermal
Water
Aq. ammonia
[49]
Pomegranate and watermelon
peel
Microwave
Water
-
[50]
Mango peel
Pyrolysis
Water
-
[51]
Lychee peel
Hydrothermal
Aq. ethanol
-
[52]
Sweet potato peel
Hydrothermal
Water
-
[53]
Durian shell
Hydrothermal
Water
-
[54]
Table 4. BCDs prepared from seeds and spices along with different synthetic routes applied.
Precursors
Method
Solvent
Additive
References
Date kernels
Hydrothermal
Water
-
[55]
Mustard seeds
Hydrothermal
Water
-
[56]
Jackfruit seeds
Microwave
Water
-
[57]
Groundnut
Hydrothermal
Water
-
[58]
Kiwi seeds, black sesame, and
white sesame seeds
Pyrolysis
Water
-
[59]
Cinnamon, turmeric, red chilli,
and black pepper
Hydrothermal
Water
-
[60]
White pepper
Hydrothermal
Ethanol
-
[61]
biological media. Following this, Long et al. prepared
dual emission CDs from white pepper with QY of
10.4% by one-pot solvothermal method [61]. Table 4
gives a list of the seeds/spices used for preparing
BCDs.
3.5. Carbon Dots Derived from Leaves and Flowers
The successful formation of BCDs from fruits and
vegetables also led to the exploration of other plant
parts like leaves and flowers. There are several reports
documented in the literature on their use as biogenic
sources for CDs synthesis.
The widely used henna leaf was taken as the carbon
source by Shahshahanipour and his co-workers for pre-
paring highly stable fluorescent CDs [62]. Henna
leaves comprise of diversified compounds ranging
from coumarins, flavonoids, gallic acid, quinines, etc.
which altogether help in carbon dot formation. The
synthesis was carried out via one-pot hydrothermal
treatment at 180ºC for 12 h with QY 28.7%. The high
value of QY was attributed to the participation of the
N-atoms during the synthesis, as confirmed by EDX.
The henna CDs showed good antibacterial activity
against E. coli and S. aureus. Water hyacinth, consid-
ered the most invasive aquatic plant, which is rich in
cellulose and therefore could serve as a good carbon
precursor. Prathumsuwan et al. prepared CDs by a two-
step acid-treated pyrolysis method [63]. The powdered
water hyacinth leaves were first digested with HNO3,
followed by pyrolysis at 250ºC for 6 h to form CDs.
The QY obtained was 27% compared to that of QY of
only 6.5% when CDs were produced without acid
treatment. CDs from gingko leaves, mint leaves, neem
leaves were also reported, all of which are prepared via
hydrothermal treatment at optimized reaction tempera-
ture and time giving QYs of 22.8%, 7.6%, 27% respec-
tively [64-66]. Both gingko and neem leaves produced
N-doped CDs and hence have higher QYs. In
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 7
Table 5. BCDs prepared from leaves and flowers along with different synthetic routes applied.
Precursors
Method
Solvent
Additive
References
Henna leaves
Hydrothermal
Water
-
[62]
Water hyacinth
Acid-treated pyrolysis
Water
-
[63]
Gingko leaves
Hydrothermal
Water
-
[64]
Mint leaves
Hydrothermal
Water
-
[65]
Neem leaves
Hydrothermal
Water
-
[66]
Aloe vera leaf gels
Microwave
Water
-
[67]
Spinach leaves
Hydrothermal
Water
-
[68]
Saffron
Hydrothermal
Water
-
[69]
Bauhinia flower
Microwave
Aq. Ethanol
-
[70]
Marigold
Acid-treated pyrolysis
Water
Ethylenediamine
[71]
Tulsi leaves
Hydrothermal
Water
-
[72]
Kalmegh leaves
Hydrothermal
Water
-
[73]
another work, CDs were produced from Aloe vera leaf
gels via microwave irradiation technique at 200ºC for 30
min, maintaining a constant pressure of 13.5 bar and
power ~25 W [67]. The presence of mucopolysaccha-
rides in the aloe flakes, obtained after the complete re-
moval of water from the leaf gel, is the carbon source for
CDs formation. Ran et al. extracted chloroplasts from
spinach leaves and underwent hydrothermal treatment at
200ºC for 2 h to generate fluorescent CDs [68].
The use of saffron, bauhinia flower, and marigold to
prepare CDs are reported [69]. Pulverized stigma saf-
fron can be a good carbon source as it contains D-
glucose and other carbohydrates. Ensafi et al. generat-
ed hydrophilic, stable CDs from saffron by hydrother-
mal route with a good QY of 23.6% [70]. Huang et al.
adopted microwave irradiation treatment (at 1000 W
for 10 min) to form N-CDs dispersed in 50% ethanol
from bauhinia flowers without any chemical modifica-
tion, obtaining an excellent QY of 27% [71]. Similarly,
tulsi and kalmegh leaves are used as carbon source [72,
73]. Table 5 gives a summarisedlist of all the leaves
and flowers used in BCDs synthesis.
3.6. Carbon Dots from Human Derivatives
Human derivatives include the use of hair and fin-
gernails for the synthesis of CDs. Both hair and finger-
nails are composed of keratin and therefore, they are a
good source of C, O, N, and S (small amount) elements
in producing heteroatom-doped CDs. Guo et al. adopt-
ed a simple, one-step thermal treatment of hair at
200ºC for 24 h to form N- doped CDs with QY of
10.75% [74]. At high temperatures, the hairs first sof-
tened and then carbonized to form CDs. Here, the yield
of CDs formed from the direct carbonization of hair is
95%, which is much higher than that of CDs obtained
from hydrothermal treatment of hair (14%). On the
other hand, Chatzimitakos et al. produced N, S co-
doped CDs using fingernails as a precursor [75]. Fin-
gernails were first treated with conc. H2SO4 and given
microwave treatment (400 W) for 2 min to obtain high-
ly fluorescent CDs with excellent QY of 42.8%. The
average relative atomic concentration was found to be
57.8% carbon, 34.8% oxygen, 5.9% nitrogen, and 1.5%
sulphur. Interestingly, the emission spectrum exhibited
dual peaks which might be reasoned due to the differ-
ent surface states created by the hetero-elements pre-
sent, resulting in the increase of radiative recombina-
tion of the electrons trapped in these surface states. Ta-
ble 6 lists the sources used in CDs synthesis.
3.7. Carbon Dots Derived from Microorganisms
The use of microorganisms in synthesizing CDs has
emerged to be a significant area of research in the mi-
crobial world. Hua and his co-workers were the first to
report the synthesis of CDs from bacteria [76]. They
used Staphylococcus aureus and Escherichia coli bac-
teria as carbon sources. In the process, the bacteria in
lysogeny broth were centrifuged and resuspended in
water to undergo hydrothermal treatment in an auto-
clave at 200ºC for 24 h. The QYs of CDs-S. aureus and
CDs-E. coli were calculated to be 7% and 8.1%, re-
spectively. Both the CDs possessed high colloidal sta-
bility because of their highly negative surface charge (-
42 mV) and therefore, they could effectively distin-
guish the dead microbial cells from the live ones. Other
studies reported the synthesis of CDs from
8 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
Table 6. BCDs prepared from human derivatives along with different synthetic routes applied.
Precursors
Method
Solvent
Additive
References
Hair
Hydrothermal
Water
-
[74]
Fingernails
Microwave
Water
-
[75]
Table 7. BCDs prepared from microorganisms along with different synthetic routes applied.
Precursors
Method
Solvent
Additive
References
Staphylococcus aureus
Hydrothermal
Water
-
[76]
Escherichia coli
Hydrothermal
Water
-
[76]
L. Plantarum LCC-605
Hydrothermal
Water
-
[77]
B. Cereus MYB41-22 cells
Hydrothermal
Water
-
[78]
Mushrooms
Hydrothermal
Water
-
[79]
Dunaliella salina
Hydrothermal
Water
-
[80]
L. plantarum LCC-605 and B. cereus MYB41-22 cells
following a similar experimental protocol as the previ-
ous one obtaining good QYs of 16% and 18.3% respec-
tively [77, 78]. All CDs possessed nitrogen elements
which might be responsible for good QYs.
Yang et al. established the green synthesis of CDs
from fungi (mushrooms) by facile one-step hydrother-
mal treatment in an autoclave at 200ºC for 6 h with QY
of 15.3% [79]. The XPS results showed the composi-
tion of CDs as 58.16% C, 9.26% O, and 30.67% N.
Dunaliella salina is a halophilic, unicellular algae
found and isolated from Sambar Lake, Rajasthan, In-
dia. Singh et al. utilized these microalgae to produce
CDs via hydrothermal treatment at 200ºC for 3 h with
QY of 8% [80]. The CDs showed some crystalline pat-
terns along the amorphous regions owing to the halo-
philic nature of the microalgae. XPS studies also
showed the presence of hetero-atoms such as N, P
along with C and O. The microorganisms used are all
summarised in Table 7.
3.8. Carbon Dots Derived from Other Miscellaneous
Biogenic Sources
Apart from the different plant parts derived carbon
dots, there are several other biogenic sources from
which CDs are synthesized. These include milk, onion
peel, prawn shell, shrimp, silkworm chrysalis, wool, to
mention a few. Onion waste is a rich source of simple
sugars and fructo-oligosaccharides that can serve as a
good carbon source. Bandi et al. utilized this onion
waste as a precursor to producing highly fluorescent
CDs by mixing with ethylenediamine in an autoclave at
120ºC and 15 lbs pressure [81]. The QY was deter-
mined to be 28% which might be due to in situ N-
passivation of CDs. Another N-CDs from silkworm
chrysalis showed a very high QY of 46% when sub-
jected to microwave radiation for 45 min, at 210ºC and
45 atm [82]. Silkworm consists of chitosan and protein,
which serve as a good source of carbon and nitrogen.
Yao and his group developed magneto-fluorescent CDs
by combining a waste crab shell with three different
transition metal ions, Gd3+, Mn2+ and Eu3+ [83]. Crab
shell contains abundant chitin, which not only can
serve as a carbon source but also can act as a chelating
agent due to the hydroxyls and acetamido functional
groups in their chemical structure. The synthesis pro-
ceeded by treating the powdered crab shell in 1% acetic
acid and mixing it with an appropriate amount of metal
salt to undergo microwave irradiation for 10 min at
210ºC. All CDs displayed high crystallinity with an
average QY of 15%. Another industrial waste produced
in large amounts during the purification of sugar is sug-
arcane molasses. They have a sugar content of 50% and
can be effectively utilized as a carbon source for CDs
production. Huang et al. employed waste sugarcane mo-
lasses to convert to CDs by heating in an autoclave at
250ºC for 12 h [84]. Similarly, Thongsai et al. synthe-
sized CDs from rice husk, another agricultural waste, in
a Teflon-lined autoclave at 200ºC for 6 h [85]. One of
the reports experimented with the doping of different
elements, other than nitrogen, in fabricating CDs. Pi-
card et al. employed a conventional heating method to
synthesize CDs from Miscanthus grass extract [86].
Miscanthus grass is a perennial plant that contains
high-quality lignocellulosic components. In the pro-
cess, the grass extract after adjusting to the pH of the
basic medium, was then heated in an oven at 180ºC for
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 9
Table 8. BCDs prepared from other miscellaneous sources along with different synthetic routes applied.
Precursors
Method
Solvent
Additive
References
Onion waste
Hydrothermal
Water
Ethylenediamine
[81]
Silkworm chrysalis
Microwave
Water
-
[82]
Crab shell
Microwave
1% acetic acid
-
[83]
Sugarcane molasses
Hydrothermal
Water
-
[84]
Rice husk
Hydrothermal
Nitric acid
-
[85]
Miscanthus grass
Pyrolysis
Water
Ethylenediamine and o-
phosphoric acid
[86]
Jute
Pyrolysis
Water
-
[87]
Egg shell
Pyrolysis
Water
-
[88]
Boswellia plant bark
Hydrothermal
Water
-
[89]
Cannabis sativa
Hydrothermal
Water
Ethylenediamine and glu-
tathione
[90]
Cranberry beans
Hydrothermal
Water
-
[91]
Gymnostemma
Pyrolysis
Water
-
[92]
Tea waste
Pyrolysis
Water
Ethylenediamine
[93]
Sandalwood
Hydrothermal
Water
-
[94]
Palm kernel
Hydrothermal
Water
Ethylenediamine
[95]
Wheat straw bamboo
Hydrothermal
Water
Urea
[96]
4 h. For doping with N, ethylenediamine was added to
the extract, whereas, for doping with P, phosphoric acid
was added. Again, for N, P co-doping, both reagents
were added to the extract to fabricate N, P-CDs. Out of
all CDs prepared, the N-CDs showed the strongest PL
emission with QY ~12%, whereas all other CDs had QY
less than 10%. Thus, N-doped CDs could act as an ex-
cellent fluorescent probe. Recently, a report showed the
formation of CDs from jute dispersed in water via one-
step pyrolysis method [87]. Jute comprises of cellulose,
hemicellulose along with lignin components and hence,
proved to be a potential carbon precursor for CDs syn-
thesis. The jute fibers were made friable by heating for a
short time at 180ºC in a muffle furnace, prior to direct
heating at 200ºC for 6 h. The as-prepared CDs were
highly fluorescent and showed the unusual excitation
wavelength-independent emission behaviour, which was
attributed to the formation of uniform surface states or
surface chemistry. There are many other sources listed in
Table 8 along with the discussed ones used as effective
carbon precursors in synthesizing dots [81-96].
4. ORIGIN OF PHOTOLUMINESCENCE
Photoluminescence (PL) is the most fascinating
property of CDs emitting different colour PL ranging
from deep ultraviolet to white light emission, depend-
ing on the synthetic routes and chemical structure of
the dots. The emission peak of CDs has large Stokes
shifts with peak position always related to the excita-
tion wavelength, known as excitation wavelength-
dependent behaviour [97]. Such kind of behaviour is
attributed to the formation of dots of variable sizes and
surface chemistry. However, there are also CDs exhib-
iting excitation wavelength-independent behavior [87].
Several studies are undertaken to understand the PL
mechanism of the CDs. Out of several reports investi-
gated, it could be found out that the mechanism of PL
can be categorised into quantum size effects, and sur-
face states [98]. Quantum size effects also referred to
as quantum confinement effect, states the dependence
of energy level or band gap on particle size and shape.
For example, Lin et al. prepared three types of CDs
with red, green and blue fluorescence that emitted un-
der single excitation [99]. The study showed the CDs
possessing similar chemical compositions but different
particle size, thereby ultimately indicating the PL emis-
sions arising from quantum confinement effect. Anoth-
er group demonstrated the relation of PL emission of
CDs with that of particle size by purifying the synthe-
sized CDs by column chromatography to obtain differ-
ent particle size with different emission colours [100].
10 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
It was shown that the energy gap between HOMO and
LUMO decreased with the increase in particle size, that
was in accordance to the previous study. More precise-
ly, the quantum confinement results from the changes
in π*-π gap occurring in the sp2 conjugated π-domains
of the carbon core.
Apart from the quantum size effects, surface state
effects also play an important role in the PL emission
mechanism of CDs. From the term surface state, it im-
plies the surface functional groups like -COOH, -OH, -
NH-, C-O-C, etc., and other dangling bonds attached
onto the CDs surface that give rise to diverse fluoro-
phores [98]. These functionalities create surface de-
fects/ traps which modulate the energy level of CDs.
Liang’s group synthesized multicolour N-doped CDs
with tunable fluorescence which depended on the sur-
face functional groups which was understood from the
introduction of new energy levels (HOMO) arising
from C=O/C=N groups, producing more electronic
transitions to the LUMO [101]. Another work reported
by Xiong et al., where eight types of CDs were sepa-
rated by column chromatography and speculated that
the PL from the CDs surface arose from the oxygen
functionalities along with conjugated carbon atoms
(Fig. 2) [102]. The studies further showed that the
emission shifts to longer wavelength when N-related
defect states are involved in electronic transitions.
Fig. (2). (A) One-pot synthesis and purification route for
CDs with distinct fluorescence characteristics, (B) Eight CDs
samples under 365 nm UV light, and (C) Corresponding PL
emission spectra of the eight samples, with maxima at 440,
458, 517, 553, 566, 580, 594, and 625 nm. Reprinted from
ACS Nano, 10 (1), Ding, H.; Yu, S. B.; Wei, J. S.; Xiong, H.
M., Full-color light-emitting carbon dots with a surface-
state-controlled luminescence mechanism, 484-491, Copy-
right (2016), with permission from [AMERICAN CHEMI-
CAL SOCIETY] [102]. (A higher resolution/colour version
of this figure is available in the electronic copy of the arti-
cle).
There are also reports that justify the PL mechanism
of CDs by synergistic effect of the quantum confine-
ment effect as well as the surface state [98]. A series of
full-colour emitting CDs were synthesized by hydro-
thermal treatment followed by purification and separa-
tion by column chromatography. It was found that the
fluorescence properties could be modulated by tuning
the sp2 carbon core and changing the surface functional
groups that give rise to defects/trap states.
5. APPLICATIONS OF BIOGENIC CARBON
DOTS
In this section, the use of biogenic carbon dots in
different sectors of applications ranging from sensing,
drug delivery and energy sector are discussed.
5.1. Bio-/Chemo-sensors
BCDs have been extensively used as fluorescent
sensors in detecting a wide range of chemical and bio-
logical entities. The response of detection is understood
in terms of the interaction of the moiety with that of the
functional groups present in biogenic CDs to create a
measurable response signal. Here, the response is an
optical signal which is recorded on the basis of the in-
crease or decrease of fluorescence intensity. The pio-
neers to utilize CDs as a sensor were Guo and his co-
workers in 2013, who synthesized CDs from sodium
citrate and used them to selectively sense Hg2+ ions in
water [103]. Different sensing mechanisms have been
proposed and are collectively based on certain princi-
ples briefly discussed. (A) Electron transfer: An inter-
nal redox reaction tends to occur between the excited
state of CDs and that of the analyte that can either do-
nate or accept electrons. This phenomenon is termed
Photoinduced Electron Transfer (PCT). (B) Energy
transfer: In this process, an excited molecule (donor),
while returning to the ground state, simultaneously
transfers energy to an acceptor in the excited state, is
referred to as Fluorescence Resonance Energy Transfer
(FRET). FRET occurs due to long-range dipolar inter-
actions through excited-state donors and acceptors.
(C) Charge transfer: More precisely known as Photo-
induced Charge Transfer (PCT), this mechanism in-
volves electron transfer between donor and acceptor
moieties for fluorescence to occur. (D) Inner filter ef-
fect (IFE): Energy emitted from CDs can be reabsorbed
by the analyte. (E) Aggregation-induced emission
(AIE): During the aggregation of CDs, energy from the
excited CDs is transferred to the ground state CDs
without radiative emission.
Following are some examples discussed whereby it
is shown how CDs derived from various biogenic
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 11
sources are utilized as sensors to detect chemical and
biological species.
5.1.1. Biosensing
There are several reports of the detection of ferric
ions, Fe3+ using CDs. Tong et al. synthesized nitrogen-
containing CDs from Bauhinia flowers via the green
microwave method without post-passivation to gener-
ate a turn 'off-on' fluorescent sensor in detecting Fe3+
and ATP sequentially [71]. The presence of Fe3+ ions
could be sensed by CDs system that could be under-
stood by the quenching of fluorescent intensity having
a satisfactory sensitivity with a LOD of 0.01 µM. Fur-
thermore, the fluorescent intensity of CDs-Fe3+ system
could be regained when adenosine triphosphate (ATP)
was added to the system. The affinity of ATP towards
Fe3+ through the formation of Fe-O-P bonds was uti-
lized to regain the fluorescence of CDs system that was
diminished in the course of detecting of Fe3+ ions.
Hereby, a 'turn-on' fluorescent ATP sensor was gener-
ated with LOD of 0.005 µM. The system was further
validated by checking with water and human serum
samples.
Coenzyme A (CoA), an essential component known
to regulate fat, sugar, and protein metabolism, is com-
monly used in clinical practice as adjuvant for the treat-
ment of uremia, chronic heparin and other chronic dis-
eases [104]. Understanding its importance, several con-
ventional techniques like HPLC, NMR, spectrophotome-
try, and fluorescence, are utilized for the detection of
Coenzyme A. Very few reports are documented in the
literature, out of which Long et al. prepared CDs from
white pepper via the solvothermal route [61]. The inter-
esting feature of the prepared CDs was that it showed
two strong fluorescence peaks at two different wave-
lengths at a single excitation wavelength, acting inde-
pendently of each other. The sensing study was carried
out via conjugating the CDs with Cu2+ ions where there
was quenching in fluorescence intensity and after com-
plexing the system with that of CoA, the fluorescence
intensity was recovered. Fig. (3) shows the representa-
tive protocol for the synthesis of ratiometric white-
pepper-derived CDs along with its sensing. In fact, the
CDs derived from white pepper acted as an excellent
ratiometric nanosensor in a way that it had particularly
'turned on' the fluorescence intensity of the emission
peak at shorter wavelengths (green emission) when CoA
was subjected to the CDs-Cu2+ system while the emis-
sion peak at longer wavelengths (red emission) hardly
had no change in its fluorescence intensity throughout
the process. This clearly justifies the sensitivity of the
analytes toward the CDs system. When studied in the
concentration range of 0-150 µM, the ratio of relative
fluorescence intensity showed an excellent linear corre-
lation with the concentrations of CoA, and the LOD was
8.75 nm. Also, the affinity of CDs-Cu2+ towards CoA
showed good selectivity in the presence of some potent
interfering agents such as cysteine, tyrosine, alanine,
leucine, tryptophan, lysine, valine etc. It was assumed
that the presence of thiol, phosphate and amino groups
in CoA could particularly conjugate with Cu2+ ions by
forming a stable complex wherein the Cu2+ ions got de-
tached from the CDs system, resulting in the recovery of
the fluorescence of the CDs.
Moreover, the strategy has been successfully ap-
plied for label-free detection of CoA in real pig liver
samples having recovery within the range of 93-108%.
Cobalamine or vitamin B12, a water-soluble vita-
min, is considered critical in the metabolism of cells
and in myelin synthesis, which is necessary for the
proper functioning of the nervous system [105]. Regu-
lar monitoring of vitamin B12 is important as an excess
amount of it leads to a shortage of folic acid in the
body, causing some serious toxic effects thereafter
[106]. Therefore, finding a compatible sensor system
for vitamin B12 is imperative. In response to its re-
quirement, Tiwari et al. synthesized highly fluorescent
nitrogen and sulphur co-doped carbon dots derived
from leaves of Cannabis sativa, where ethylene dia-
mine and glutathione acted as nitrogen and sulphur
sources, respectively, to enhance the fluorescence
property of the CDs [107]. The effect of vitamin B12
on the fluorescent behaviour of the CDs was checked
and 'turn-off' fluorescence was observed in the range of
0-550 µg mL-1 with gradual quenching of fluorescent
intensity. The linear response was found between 20
and 100 µg mL-1 with LOD of 7.87 µg mL-1. The selec-
tivity of the CDs system towards the analyte was also
assessed in the presence of other vitamins and amino
acids and showed no interference in the fluorescent
behaviour. The fluorescence lifetimes of CDs with and
without vitamin B12 were similar, which implied that
the sensing behaviour was purely static in nature. The
study demonstrated the superiority of biogenic carbon
dots in terms of broader linearity and low LOD value
compared to other CDs systems prepared from sources
other than biogenic ones [108]. The practical applica-
bility was also checked with pharmaceutical injections
of varying concentrations of vitamin B12.
5.1.1.1. Electrochemical Biosensing
Electrochemical biosensing is another common
pathway of sensing technique where the designed sys-
tem is based on converting the biochemical events to
12 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
Fig. (3). Protocol of white-pepper derived CDs along with its sensing study. Reprinted from Food Chemistry, 315, Long, R.;
Guo, Y.; Xie, L.; Shi, S.; Xu, J.; Tong, C.; Li, T., White pepper-derived ratiometric carbon dots for highly selective detection
and imaging of coenzyme A, 126171-126177, Copyright (2020), with permission from [ELSEVIER] [61]. (A higher resolu-
tion/colour version of this figure is available in the electronic copy of the article).
electrical signals. The biochemical events may range
from enzyme-substrate reactions or antigen-antibody
interaction, wherein their responses will be generated by
amperometry, impedimetry, potentiometry, or by volt-
ammetry, including square wave voltammetry (SWV),
differential pulse voltammetry (DPV), cyclic voltamme-
try (CV), anodic stripping voltammetry (ASV) [109]. In
essence, an electrochemical biosensor comprises of two
components: (a) a biological recognition element and (b)
a physicochemical transducer system [110]. These
builds up the most important key component, that is, the
working electrode, which is used as a solid support for
immobilizing biomolecules such as enzymes, antibodies,
nucleic acids. Electrochemical biosensors combine the
high specificity of biorecognition agents with the sensi-
tivity of transduction methods and so appropriate immo-
bilization of biomolecules is necessarily such that it may
not cause loss of activity, sensitivity and selectivity to
reduce the overall efficiency of the system [109]. Never-
theless, a reference electrode and sometimes, a counter
electrode are also used in the electrical measurement set-
up. CDs possess electron-donor and acceptor properties
and therefore are extensively used in electrochemical
biosensing. The idea behind the use of CDs is that they
can directly interact with target analytes to influence the
electrochemical signals of electrodes [111]. As a result,
CDs can be loaded onto the electrode surface, and the
altered signals (i.e., current) due to the interaction of
CDs with biomolecules are collected for the detection
and analysis of the target analytes. Electrochemical de-
tection techniques using CDs are grabbing interest
amongst other sensing techniques because of the rapid
response time, high sensitivity, and feasibility for com-
mercialization. Following are some examples discussed
where CDs are used as electrochemical biosensing for
the detection of some important biomolecules.
Among the catecholamines, dopamine (DA) acts as
an important neurotransmitter and chemical messenger
in the brain. The normal range of DA in human body lies
from 10-8 to 10-6 M [112]. Fluctuation in the said range
is known to cause neurological and neurodegenerative
disorders such as Parkinson's disease, attention-deficit
hyperactivity disorder (ADHD), and Huntington's dis-
ease [113]. This necessitates the monitoring of DA in
physiological fluids. There are several reports of dopa-
mine sensing mainly by electrochemical methods. The
reason behind is DA possesses inherent redox activity
and so can easily be oxidised on the electrode [114].
Jiang et al. synthesized N-doped CDs from collagen
by hydrothermal method and loaded on a bare glassy
carbon electrode by Nafion solution to form NCDs
modified glass carbon electrode (NCD/GCE) [115].
Electrochemical impedance spectroscopy (EIS) was
used to characterize the interfacial electrical properties
of the modified electrodes. The CV curves and the cor-
responding Nyquist plot of the designed electrode
showed excellent charge transfer proving it to be an
electrical conducting material. The next step was car-
ried out by introducing DA as the guest molecule to
verify the recognition ability of NCDs. DPV is used to
detect DA via NCD/GCE, which showed that upon in-
creasing the concentration of DA, the oxidation peak
current improves significantly, suggesting that the re-
sponsiveness of the NCDs/GCE towards DA. The an-
odic peak current of DA shows a good linear relation-
ship with DA concentration in the range from 0 to 1
mM. LOD is evaluated to be 10-9 M. The system also
exhibited good selectivity and sensitivity for DA detec-
tion in the presence of the two most common species
like uric acid and ascorbic acid obtained via DPV
measurements.
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 13
Another work reported for the selective detection of
dopamine was by fabricating an electrode based on
CDs decorated 3D CuO nanorods (CR@CD) modified
lead pencil (LP) [116]. The CDs were prepared from a
biogenic source, orange peel via a hydrothermal ap-
proach. In the experiment, the electrochemical set-up
was a three-electrode system consisting of platinum
wire as the counter electrode, Ag/AgCl as the reference
electrode, and CR@CD modified LP as the working
electrode. The use of CuO nanorods lies in the fact that
they have high electrocatalytic activity by expounding
a greater fraction of active catalytic sites and short dif-
fusion pathways. The electrochemical efficiency was
further improved after decorating the CR with CDs by
aiding as an electron transport mediator and generating
more surface defects. CR@CD could sense the pres-
ence of DA over a good linear range of 5–2250 µM
with LOD of 0.0007 µM and sensitivity of 5.24 µAµM-1.
The selectivity of the designed electrode towards DA in
the presence of other prominent co-existing interfering
biomolecules such as uric acid, ascorbic acid, glucose,
glycine, L-cysteine was also evaluated through DPV
and amperometry measurements. Finally, the electrode
demonstrated good efficacy in monitoring spiked DA
from deboned chickens, suggesting the real-time use of
the electrode for commercialisation.
There has been a growing interest in detecting target
DNA due to its importance in pharmaceuticals and
clinical diagnosis. Huang et al. reported an ultrasensi-
tive electrochemical biosensor for determining target
DNA [117]. For the fabrication of the electrode, a
nanocomposite was prepared by immobilizing CDs on
Pd-Au nanoalloy. Pd-Au nanoalloy is known to possess
high surface area and excellent conductivity. On the
other hand, CDs synthesized from banana peels by mi-
crowave treatment without the use of any surface pas-
sivating agent, also turned out to be highly conducting.
The nanocomposite was then cast on a glassy carbon
electrode surface to form Pd-Au@CDs/GCE. For the
determination of the target DNA, it was embedded on
the Pd-Au@CDs/GCE covalently via coupling of the
negative carboxyl group of CDs and with the amino
groups on the DNA probe. Cyclic voltametric and elec-
trochemical impedance spectroscopy behaviour of the
electrodes were studied, where it was shown that the
reduction and oxidation peak currents and the electrode
transfer resistance value was shown to be the highest
for the fabricated electrode compared to that of the oth-
er counterparts such as CDs/GCE, Pd/GCE or
Au/GCE. Methylene blue (MB) has been widely ap-
plied for DNA hybridization as an electrochemical in-
dicator due to its interaction with guanine. In the hy-
bridization experiment, the system showed a wide
range from 5×10–16 to 1×10−10 mol L−1 for the target
DNA concentrations with the LOD of 1.82×10–17 mol
L−1. Finally, the biosensor could establish its efficiency
in a real sample, the target DNA in human serum sam-
ples. A lower concentration of target DNA (2.0×10–11
mol/L) could be detected in human serum, proving its
analytical performance.
5.1.2. Chemo-sensing
Oxytetracycline (OTC) is a type of antibiotic that is
commonly used as a veterinary drug to prevent animal
disease due to its affordability and antibacterial proper-
ties [118]. However, the widespread use of OTC in
foods of animal origin has caused concerns about the
level of unsafe residues in food such as honey, meat,
and milk, as these residues pose a threat to public
health. Therefore, the detection of trace levels of OTC
in such consumables is important Liu et al. designed a
novel fluorescence probe for the sensitive detection of
oxytetracycline (OTC) with the help of CDs derived
from sweet potato peels synthesized hydrothermally
[119]. The uniqueness of this work lies in the coating
of the CDs with molecular imprinted polymer (MIP),
which further enhances the recognition capability to-
wards analytes due to the presence of recognition sites.
The quenching of CDs occurred when MIP-coated CDs
interacted with OTC and the mechanism was explained
due to electron transfer-induced fluorescence quench-
ing. The recognition ability of MIP-coated CDs was
investigated by testing other tetracycline analogs, such
as chlorotetracycline (CTC) and tetracycline (TC),
where the maximum affinity of MIP-coated CDs was
found only towards OTC as indicated by the high im-
printing factor value compared to that of other analogs.
The LOD of OTC was calculated to be 15.3 ng mL-1.
The fluorescence probe was successfully applied in
honey, with recoveries ranging from 90.2% to 97.3%.
This work explores the development of fluorescent
MIPs for potential applications as sensors.
Methotrexate (MTX) is an important anticancer,
chemotherapeutic drug and immunosuppressive in or-
gan transplantation, used in the therapy of solid tu-
mours, leukaemia, bone cancer, severe asthma and
rheumatoid arthritis [120]. Unfortunately, it is also a
cytotoxic compound that acts in neoplastic cells and
tissues causing serious side effects like cardiotoxicity,
vomiting, diarrhoea, and hepatotoxicity, among a few
[121]. Therefore, monitoring the MTX levels in a pa-
tient's blood for optimization of drug dose and achiev-
ing the best therapeutic effect accurately is of utmost
necessity. Rezaei and his co-workers developed a low-
14 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
cost, facile, one-pot hydrothermal synthesis of CDs
derived from the Lawsonia inermis (Henna) plant that
acted as a biocompatible probe for the detection of
MTX drugs [62]. The response was such that there was
a gradual decrease in the fluorescence intensity of the
CDs when MTX having a concentration range of 0-18
µmolL-1 was added to the system. The mechanism of
quenching was suspected as FRET as the MTX mole-
cules have a broad absorption spectrum that overlapped
with that of the emission window of CDs, whereby
MTX is considered to act as an acceptor (quencher) of
the CDs (donor). The system showed good analytical
performance, where the quenching response showed
linearity in the range of 0.02-18 µmolL-1 with LOD of
7 nmol L-1. The system also had good selectivity in the
presence of interfering agents such as tryptophan, me-
thionine, ascorbic acid, glucose, dopamine, KCl, FeCl3
etc. The practical applicability of the proposed system
for determining trace amounts of MTX was carried out
with human blood plasma, with an outcome of ac-
ceptable precision and reliability for the determination
of MTX in serum samples.
Numerous chemicals are found in cosmetics and
health-care products, which common people, especially
in underdeveloped countries, are ignorant of the fact
that they are carcinogenic. Many of the ingredients
cause skin irritation, endocrine disruption, and repro-
ductive toxicity [122]. Some of these chemicals are
para-aminobenzoic acid (PABA), parabens (used as a
preservative), benzophenone (BP), and hydroquinone
(HQ). Deb and her co-workers synthesized highly fluo-
rescent CDs from aloe vera gel and incorporated them
into a film consisting of alginate and Aloe vera gel it-
self to form a nano-bioconjugate film [67]. The film
could detect the presence of structurally similar car-
cinogenic chemicals found in cosmetics such as PABA,
HQ, BP, and PP by acting as an optical turn-off sensor.
All of these chemicals, when studied in the range of
10-8 to 10-3 M showed gradual quenching of the fluo-
rescent CDs. The system had a linear detection range of
5X10-4 to 10-6 M. The mechanism of the fluorescent
quenching was explained via an electron transfer pro-
cess where the CDs in the act as electron donor and the
analytes as electron acceptors. The nano-bioconjugate
film showed satisfactory results in detecting these haz-
ardous chemicals in some locally purchased cosmetic
samples.
5.2. Bioimaging
Apart from the inherent fluorescence properties,
certain characteristic features such as high aqueous
solubility, good photostability, higher resistance to
photobleaching, great biocompatibility, and low cyto-
toxicity of CDs make them potential candidates for
nano-bioimaging in biological applications. There are
several reports of CDs derived from biogenic sources
that are involved not only in cellular imaging but also
bacterial, fungal, and other in vivo imaging. A few of
them are discussed below:
Banana peel is a common solid biowaste. Atchudan
et al. prepared CDs from these banana peels hydro-
thermally that turned out to have intense fluorescence
with excellent photostability and biocompatibility
[123]. The heteroatoms like nitrogen and oxygen pre-
sent in the CDs with varied functionalities are said to
contribute towards the good fluorescence nature. These
as-synthesized CDs were used for in vivo bioimaging in
nematodes. The CDs were first internalized into the
nematodes and labeled not only the cell membrane but
also into the whole body of nematodes and brightly
illuminated the multicolour emissions by varying the
excitation wavelength (Fig. 4). The characteristic of
CDs exhibiting excitation-dependent fluorescence
emission is the reason behind CDs acting as a multi-
colour nanoprobe in imaging studies.
In another study done by Bhamore et al., water-
dispersible multicolour emissive C-dots were obtained
from Manilkara zapota (sapodilla) fruit for imaging of
bacterial and fungal cells [124]. The emission of CDs
was well-tuned by sulphuric acid and phosphoric acids
that resulted in generating blue, green, and yellow CDs.
These CDs proved to exhibit non-toxic nature on HeLa
cells by MTT assay. The application of three CDs in
cell imaging was evaluated by using E. coli (bacteria),
Aspergillus aculeatus (fungi), and Fomitopsis sp. (fun-
gi) cells as a model. It can be seen in the figure (Fig. 4)
that three kinds (blue, green, and yellow) of CDs have
provided blue, green, and red colour fluorescent signals
at different excitation wavelengths with good intensity
for cell imaging. It was found that these CDs got easily
internalized into E. coli, Aspergillus aculeatus,
and Fomitopsis sp. cells via cell membrane through
endocytosis. It could also be noticed that the CDs were
located in the cell membrane as well as the cytoplasm.
There were no such fluorescence signals in the cells
without CDs, emphasizing on the smaller size and high
degree of distribution of the CDs that got easily pene-
trated into the cells, resulting in imaging cells with
bright fluorescent signals.
Besides, there are reports where CDs could distin-
guish between live and dead microbial cells by the im-
aging technique. Qin et al. synthesized CDs from E.
coli BW25113 using a hydrothermal method and could
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 15
Fig. (4). (a) Toxicity assay of nematode incubation with different concentrations of synthesized CQDs. Multicolor imaging of
in vivo model nematode incubation with CDs (100 µg mL-1) under the excitation wavelength of (b) 400 nm, (c) 470 nm, (d) 550
nm, (e) bright-field (BF) and (f) merge (overlap). Reprinted from Physica E: Low Dimensional Systems and Nanostructures,
126, Atchudan, R.; Edison, T. N. J. I.; Shanmugam, M.; Perumal, S.; Somanathan, T.; Lee, Y. R., Sustainable synthesis of car-
bon quantum dots from banana peel waste using hydrothermal process for in vivo bioimaging, 114417, Copyright (2021), with
permission from [ELSEVIER] [123]. (A higher resolution/colour version of this figure is available in the electronic copy of the
article).
be successfully used as a fluorescent probe for bioim-
aging both in vitro (microbial and cells) and in vivo
(mice) [125]. It was observed that CDs-E. coli can se-
lectively stain dead microbial cells (bacteria and fungi)
but not live cells due to their highly negative zeta po-
tential and size. Bacillus cereus (B. cereus, bacteria)
and Saccharomyces cerevisiae (S. cerevisiae, fungi)
were used in this study. In the in vivo imaging study, a
mouse skin and tissues could be effectively permeated
by fluorescent CDs. Images were captured at different
time intervals up till the 24th hour. At initial hours,
clear and strong fluorescence signals in the intestine,
bladder region, and back of mice were observed after
the injection. At later hours, the fluorescence signals
shifted the focus more in the intestinal part, gradually
weakening the bladder regions, and finally after 24
hours, the fluorescence intensity almost got disap-
peared from the lower region (Fig. 5). These clearly
indicate that the CDs possess strong biocompatibility
and excellent penetrating factor and could be rapidly
excreted from mice through the intestines. This study
could demonstrate the CDs cross the blood-brain barri-
er which is always a challenging task. The smooth
crossing of the blood-brain barrier by CDs could be
explained by the very small size, the presence of a
large number of functional groups on the CDs' surface,
and the strong affinity with the endothelial cell mem-
brane of the blood-brain barrier.
A group of researchers carried out studies on image-
guided photodynamic therapy (PDT), which remains a
considerable challenge for cancer therapy. In this work,
CDs derived from lychee exocarp were prepared and
treated with polyethylene glycol followed by conjugat-
ing with chlorin e6 (Ce6) and transferrin (Tf) (Fig. 6)
[126]. The role of post-treatment with various mole-
cules to design this nanoprobe is that the CDs act as the
photosensitizer carrier and light-emitting source for
imaging, and Tf as the navigation molecule. Ce6 was
used as a fluorescence receptor. Moreover, this func-
tional nanoprobe emits fluorescence in the NIR region,
shows very low biological toxicity, and, therefore, can
minimize side effects on normal cells. Thus, this dual-
function nanoprobe made from a biogenic source can
be used as a specific agent for NIR fluorescence
16 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
Fig. (5). In vivo imaging of male BALB/c mice after intraperitoneal injection of CDs. (a) Fluorescence images of mouse bodies
from the back view. (b) Fluorescence images of mouse bodies from the abdominal view. Reprinted from Analyst, 145 (1), Qin,
K.; Zhang, D.; Ding, Y.; Zheng, X.; Xiang, Y.; Hua, J.; Wei, Y., Applications of hydrothermal synthesis of Escherichia coli
derived carbon dots in in vitro and in vivo imaging and p-nitrophenol detection, 177-183, Copyright (2020), with permission
from [ROYAL SOCIETY OF CHEMISTRY] [125]. (A higher resolution/colour version of this figure is available in the elec-
tronic copy of the article).
Fig. (6). Schematic representation of the fabrication and application of CDs and nanoprobe. Reprinted from Nanoscale, 10 (38),
Xue, M.; Zhao, J.; Zhan, Z.; Zhao, S.; Lan, C.; Ye, F.; Liang, H., Dual functionalized natural biomass carbon dots from lychee
exocarp for cancer cell targetable near-infrared fluorescence imaging and photodynamic therapy, 18124-18130, Copyright
(2018), with permission from [ROYAL SOCIETY OF CHEMISTRY] [126]. (A higher resolution/colour version of this figure
is available in the electronic copy of the article).
imaging and PDT. In the process, the nanoprobe enters
the tumour cells through Tf mediated endocytosis and
achieves targeted NIR fluorescence imaging of tumour
cells and tumour tissues of mice based on the fluores-
cence resonance energy transfer (FRET) between the
CDs and Ce6. Consequently, with the aid of this imag-
ing, the photosensitizer (Ce6) on the CDs' surface re-
lease singlet oxygen (1O2) molecules through photo-
dynamic reactions, killing cancer cells, and resulting in
the PDT of tumour cells and tissues. This work pro-
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 17
vides new prospects for utilizing biogenic carbon dots
in designing PDT systems.
5.3. Drug Delivery
CDs derived from biogenic sources have also
gained attention in drug delivery applications. Apart
from engaging in real-time tracking and sensing abili-
ties owing to their fluorescent nature, biogenic CDs are
biocompatible agents and provide safety and water sol-
ubility features. One of the disadvantages of conven-
tional drug delivery is the lack of target specificity, and
rapid release of drugs, resulting in a reduction of thera-
peutic efficiency and, inefficiency in loading hydro-
phobic drugs. The use of nanomaterials in drug deliv-
ery via conjugating drugs with nanomaterials or nano-
composite systems has fulfilled the requirement of tar-
geted drug delivery resulting in an overall enhancement
of drug absorption, distribution, metabolism, and elim-
ination [127]. Therefore, nanomaterial-based targeted
drug delivery offers several benefits, such as channel-
ling the progress of drug release with the help of imag-
ing agents on the drug carrier, transportation of mac-
romolecule drugs, delivery of multiple drugs simulta-
neously, improved drug delivery of hydrophobic drugs,
and targeted drug delivery to a specific cell, tissue, or
organ [128]. Following are some examples that discuss
the role of these CDs as sensing and tracing probes,
photo-activated antimicrobial agents, antioxidants, and
neurodegenerative agents.
In a study reported by Fahmi et al., carbon dots syn-
thesized from waste bamboo leaves (Gigantochloa
apus) were simultaneously used as a staining agent and
doxorubicin delivery to target cancer cells [129]. The
synthesized CDs were modified with 4-carboxybenzyl-
boronic acid (CBBA) to obtain specific targeting of
HeLa tumour cells. Boronic acids have a high affinity
for cis-diol moieties in sialic acid (folate receptors),
which generally exist on the membrane of tumour cells
[130]. Therefore, CBBA can specifically guide CDs to
tumour cells. The resulting modified CDs were charac-
terized using different analytical techniques, retaining
biocompatibility, nontoxicity, and stability over a wide
range of pH values and at high ionic strengths. Then,
CBBA-CDs were physically conjugated with the tu-
mour cell drug Doxorubicin (Dox) to determine the
Dox delivery ability of the CDs. To investigate the CDs
in delivering dox, confocal laser scanning microscopy
(CLSM) was done to evaluate the cellular uptake of
CDs by HeLa tumour cells. The red fluorescence of
Dox-loaded CBBA-CDs, which is the characteristic
emission of Dox, shown in CLSM observed in the nu-
clei of cells proves the successful delivery of Dox drug
in tumour cells. Dox operates as a tumour drug by dis-
turbing the DNA helix structure in the cell nucleus.
This demonstrates the cellular pathway for entering
HeLa cells via folate receptor-mediated endocytosis.
Besides, cell viability and flow cytometry results con-
firmed the selective uptake of CD by HeLa cells, sig-
nificantly enhancing the cell cytotoxicity.
In another study, carbon dots (CDs) were prepared
from Daucus carota subsp. Sativus (carrot) roots via
one-step hydrothermal method, were used as nanovesi-
cles for delivery of mitomycin drug [131]. The success-
ful loading of mitomycin drugs in the synthesized CDs
was understood by FT-IR spectroscopy that suggested
non-covalent interactions, more specifically via hydro-
gen bonding. The release of mitomycin from mitomy-
cin-loaded CDs took efficiently in the mildly acidic
tumour extracellular microenvironment (pH ~6.80) via
disruption of hydrogen bonding between mitomycin
and the CDs. Besides, the smaller size, high surface-to-
volume ratio, and biocompatible nature of the synthe-
sized CDs has led to the internalization of mitomycin-
CDs into MCF-7 and Bacillus subtilis cells with high
degree. Thus, it can be concluded that the mitomycin
loaded CDs system demonstrated stimuli-responsive
behaviour, that is, pH-dependent mitomycin release
and that effectively entered into the cells.
Similarly, Shao et al. prepared CDs from medicinal
mulberry leaf (Morus alba L.) residues without any
post-treatment and used it in both intracellular imaging
of human hepatocellular carcinoma cells (HepG2) and
as drug carriers of Lycorine, anti-cancer alkaloid ex-
tracted from bulbs of Lycoris radiata L. [132]. The
presence of plentiful hydrophilic groups on the surface
of CDs could serve as sites for binding extrinsic mole-
cules/biomolecules via covalent or non-covalent inter-
actions.
There are reports of a study where CDs derived
from persimmon fruit were synthesized free of solvent
via one-pot hydrothermally [133]. The high aqueous
solubility due to the presence of numerous polar func-
tional groups renders the loading/attachment of anti-
cancer drugs, doxorubicin and gemcitabine, efficiently
onto the surface of CDs via amide formation. The drug-
loaded CDs nanohybrids showed significant anticancer
effects on HeLa cancer cells in a dose-dependent man-
ner. It was proposed that the anticancer activity of na-
nohybrids is strongly associated with the induction of
apoptosis by the mitochondrial pathway, caspase 3 ac-
tivity, and that mediates with the production of reactive
oxygen species (ROS), thereby supporting the cellular
uptake and anticancer activity of the CDs.
18 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
Fig. (7). Schematic representation of the fabrication protocol of the hybrid cotton patch and drug release study under pH 5 and
pH 7. Reprinted from ACS Sustainable Chemistry and Engineering, 8 (19), Deb, A.; Konwar, A.; Chowdhury, D. pH-
responsive hybrid jute carbon dot-cotton patch, 7394-7402, Copyright (2020), with permission from [AMERICAN CHEMI-
CAL SOCIETY] [87]. (A higher resolution/colour version of this figure is available in the electronic copy of the article).
Another study illustrated the incorporation of CDs
into a biopolymeric chitosan hydrogel-coated hybrid
cotton patch that demonstrated stimuli-responsive drug
delivery behaviour (Fig. 7) [87]. Jute was chosen as the
carbon source to synthesize highly fluorescent CDs
dispersed in water. An herbal formulation in terms of
neem leaf extract was taken as a model drug to carry
out the release studies. The stimulus chosen for the sys-
tem was pH; that is, the drug release pattern was stud-
ied at two different pH environments, pH 5 and 7. Re-
alizing the fact that an increase in pathogenic concen-
tration leads to a drop in pH value, therefore the greater
release of drug at lower pH is more desirable than that
at higher pH. So, when drug-loaded jute CDs were in-
corporated into the hybrid cotton patch and studied its
release behaviour, the release was shown to be more at
pH 5 rather than at pH 7, thereby fulfilling the re-
quirements of pH-responsive behaviour. Other CDs
derived from tea, aloe vera, ascorbic acid, and, gra-
phene oxide, when incorporated into the hybrid cotton
patch and studied its release behaviour, none of them
were responsive towards two pH environments. This
study not only shows the controlled delivery owing to
the presence of CDs, but also reflects the influence of
functional groups present on the surface of CDs in re-
sponding towards different stimuli. Such type of hybrid
cotton patches can have prospects as a smart wound
dressing material.
5.4. Catalysis and Energy Applications
The exploration of CDs derived from biogenic
sources was further extended towards electrocatalysis,
such as catalysis of the oxygen reduction reactions
(ORRs) used in fuel cells, catalysis of hydrogen pro-
duction by splitting water and also energy storage de-
vices.
There are examples of carbon dots derived from bi-
ogenic sources such as soy milk [134] and grass [135],
demonstrating its potential as ORR electrocatalyst.
These studies, however, have indicated the limitation
of BCDs to directly use as an electrocatalyst because of
its hydrophilic functional groups onto the surface of
BCDs leading to poor stability and deposition on glassy
carbon electrode. In order to overcome this, a template-
assisted method was proved to be an efficient approach
for fabricating systems with BCDs to act as efficient
ORR electrocatalyst. In a work reported by Liu et al.,
3D N-doped porous carbon materials have been gener-
ated via template-assisted high temperature pyrolysis
approach using shrimp-shell derived N-doped carbon
dots (Fig. 8) [136]. In the process, the synthesized car-
bon dots were mixed with surface acidification treated
SiO2 spheres (acting as a template) to form a N-
CNs@SiO2 composite, followed by high temperature
pyrolysis and acid treatment to generate the 3D N-
doped porous carbon material. The experimental re-
sults demonstrated best ORR catalytic activity of the
as-synthesized material with an onset potential of 0.06
V, a half wave potential of 0.21 V and a large limiting
current density of 5.3 mA cm2 (at 0.4 V, vs. Ag/AgCl)
compared to that of the commercial Pt/C catalyst with
an onset potential of 0.03 V, a half wave potential of
0.17 V and a limiting current density of 5.5 mA cm2 at
0.4 V. The high ORR performance of the material can
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 19
be attributed to the heteroatom doping, high surface
area, obtained from the carbon dot, and high graphitic
content owing to high temperature pyrolysis. Thus, the
study portrays the use of biogenic carbon dots in gen-
erating 3D N-doped porous carbon material to act as
metal-free ORR electrocatalyst with excellent electro-
catalytic activity, and high resistance to methanol
crossover oxidation reaction.
Fig. (8). Illustration of the preparation process of the 3D
NPC material. Reprinted from Physical Chemistry Chemical
Physics, 18 (5), Liu, R.; Zhang, H.; Liu, S.; Zhang, X.; Wu,
T.; Ge, X.; Wang, G. Shrimp-shell derived carbon nanodots
as carbon and nitrogen sources to fabricate three-dimensional
N-doped porous carbon electrocatalysts for the oxygen re-
duction reaction, 4095-4101, Copyright (2016), with permis-
sion from [ROYAL SOCIETY OF CHEMISTRY] [136]. (A
higher resolution/colour version of this figure is available in
the electronic copy of the article).
Another sector of energy applications is the fabrica-
tion of cheap Pt-free catalysts for hydrogen evolution
reaction (HER). Li et al. reported the use of gingko
leaves to synthesize N-doped CDs and functionalised
with ruthenium hydrothermally with RuCl3 (Fig. 9)
[137]. The resulting hybrid material demonstrated ex-
cellent catalytic behaviour under extreme alkaline con-
ditions (1 M KOH) with an onset overpotential of 0
mV and activity superior to Pt at 10 mA cm−2, proving
it to be a robust electrocatalyst for the HER.
For energy storage, graphene-based architectures
have been extensively used as supercapacitors. Inspite
of high electrical conductivity and physicochemical
stability, certain problems of graphene sheets being
prone to aggregation and restacking results in the de-
crease of ion-accessible surface area and ion transport
rate [138]. Literature reports the use of CDs in carbon
and metal oxide-based supercapacitors. Due to the
presence of various functionalities like hydroxyls, car-
bonyls, carboxyls, CDs have the ability to form intri-
cate networks in graphene-based composite electrodes,
thereby enhancing the ion-accessibility and migration
rate during charging-discharging process [139].
In a work reported by Xu et al., biogenic carbon
dot/graphene composite film (CDGF) was designed
that worked as a flexible supercapacitor electrode with
an electrodeposited NiCo2S4 layer [140]. The biogenic
source chosen was the waste fibreboards (containing 12
wt% urea-formaldehyde resin adhesive), implying the
CDs intrinsically doped with N heteroatom. The result-
ing ternary composite electrodes of CDGF/NiCo2S4
showed an ultrahigh capacitance of 1348 F g−1 at a cur-
rent density of 0.5 A g−1. The material had a capaci-
tance retention of 80.4% after 10000 charg-
ing/discharging cycles, hence exhibiting excellent cy-
cling stability and mechanical flexibility.
Fig. (9). Illustration of the synthesis of the Ru@CQDs electrocatalyst. Reprinted from Advanced Materials, 30(31), Li, W.;
Liu, Y.; Wu, M.; Feng, X.; Redfern, S. A.; Shang, Y.; Yang, B. Carbon-quantum-dots-loaded ruthenium nanoparticles as an
efficient electrocatalyst for hydrogen production in alkaline media, 1800676, Copyright (2018), with permission from
[WILEY] [137]. (A higher resolution/colour version of this figure is available in the electronic copy of the article).
20 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
6. CHALLENGES AND FUTURE PROSPECTS
The use of biogenic sources as carbon precursors in
synthesizing carbon dots not only serves as an envi-
ronmentally benign and viable source but also can be
used as dopants for various heteroatoms to prepare het-
eroatom-doped carbon dots. However, these biogenic
carbon dots suffer from low production yield. There-
fore, an approach towards advanced synthetic tech-
niques is necessary for generating BCDs with greater
production yield. In terms of quality, approach and op-
timization towards synthesizing BCDs with narrow size
distribution is necessary for efficient imaging applica-
tions in biomedical sector. More effort also has to be
laid on the optical performance of BCDs. Attempts
should be made such that the BCDs possess absorbance
and emission range in NIR region. Such BCDs would
possess low biological toxicity and would be helpful in
targeted imaging in live or diseased cells as the NIR
light can deep penetrate into tissues without ay dam-
age. Moreover, it would be helpful in improving photo-
catalytic performance as more number of photons
could be harvested in a wider optical range. In terms of
electrical applications, research on BCDs needs more
improvement, because of large heterogeneity of precur-
sors. Therefore, chemical stability needs to be evaluat-
ed for BCDs.
CONCLUSION
In this review, the importance of biogenic carbon
dots (BCDs) is emphasized. The use of biogenic carbon
dots (BCDs) has several advantages like chemical in-
ertness, low cytotoxicity, and good biocompatibility
enabling the BCDs to be used in both biomedical and
energy applications. Biogenic carbon dots (BCDs) have
the ability to convert low-value biomass or agricultural
or industrial waste into valuable materials, reducing
environmental waste. In general, carbon dots synthe-
sized from other sources suffer from low quantum yield
(<10%), and in order to enhance it, an additional step
of doping heteroatom(s) is required during synthesis.
However, the inherent presence of heteroatoms such as
nitrogen and/or sulfur in some natural products leads to
high-quality BCDs with improved optical properties
and quantum yield, eliminating the extra step of het-
eroatom doping and an easy-to-synthesize protocols. In
addition, the different phytoconstituents and bioactive
components present in the biogenic materials provide
exposure to various functional groups and adaptability
to dopants and solvents, making them potential materi-
als to synthesize BCDs. As a result of advantages listed
above there is more focus to synthesize biogenic car-
bon dots (BCDs). Several natural precursors and
sources, including fruits, vegetables, other plant-
derived parts, human derivatives, microorganisms, and
biomass wastes, were successfully utilized in obtaining
BCDs. Finally, BCDs find large applications in Bio-
sensing, Chemo-sensing, Bioimaging, Drug delivery,
Catalysis and Energy storage.
LIST OFABBREVIATIONS
CDs = Carbon Dots
PGP = Peach Gum Polysaccharide
S = Sulphur
N = Nitrogen
PL = Photoluminescence
PCT = Photoinduced Electron Transfer
FRET = Fluorescence Resonance Energy Transfer
PCT = Photo-induced Charge Transfer
CONSENT FOR PUBLICATION
Not applicable.
FUNDING
None.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial
or otherwise.
ACKNOWLEDGEMENTS
Declared none.
REFERENCES
[1] Xu, X.; Ray, R.; Gu, Y.; Ploehn, H.J.; Gearheart, L.; Raker,
K.; Scrivens, W.A. Electrophoretic analysis and purification
of fluorescent single-walled carbon nanotube fragments. J.
Am. Chem. Soc., 2004, 126(40), 12736-12737.
http://dx.doi.org/10.1021/ja040082h PMID: 15469243
[2] Wang, Y.; Hu, A. Carbon quantum dots: Synthesis, proper-
ties and applications. J. Mater. Chem. C Mater. Opt. Elec-
tron. Devices, 2014, 2(34), 6921-6939.
http://dx.doi.org/10.1039/C4TC00988F
[3] Hou, J.; Cheng, H.; Yang, C.; Takeda, O.; Zhu, H. Hierar-
chical carbon quantum dots/hydrogenated-γ-TaON hetero-
junctions for broad spectrum photocatalytic performance.
Nano Energy, 2015, 18, 143-153.
http://dx.doi.org/10.1016/j.nanoen.2015.09.005
[4] Mansuriya, B.D.; Altintas, Z. Carbon Dots: Classification,
properties, synthesis, characterization, and applications in
health care—an updated review (2018–2021). Nanomateri-
als, 2021, 11(10), 2525.
http://dx.doi.org/10.3390/nano11102525 PMID: 34684966
[5] Liu, H.; Ye, T.; Mao, C. Fluorescent carbon nanoparticles
derived from candle soot. Angew. Chem. Int. Ed., 2007,
46(34), 6473-6475.
http://dx.doi.org/10.1002/anie.200701271 PMID: 17645271
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 21
[6] Yang, Z.; Xu, M.; Liu, Y.; He, F.; Gao, F.; Su, Y.; Wei, H.;
Zhang, Y. Nitrogen-doped, carbon-rich, highly photolumi-
nescent carbon dots from ammonium citrate. Nanoscale,
2014, 6(3), 1890-1895.
http://dx.doi.org/10.1039/C3NR05380F PMID: 24362823
[7] Zheng, L.; Chi, Y.; Dong, Y.; Lin, J.; Wang, B. Electro-
chemiluminescence of water-soluble carbon nanocrystals
released electrochemically from graphite. J. Am. Chem.
Soc., 2009, 131(13), 4564-4565.
http://dx.doi.org/10.1021/ja809073f PMID: 19296587
[8] Yang, Z.; Li, Z.; Xu, M.; Ma, Y.; Zhang, J.; Su, Y.; Gao, F.;
Wei, H.; Zhang, L. Controllable synthesis of fluorescent
carbon dots and their detection application as nanoprobes.
Nano-Micro Lett., 2013, 5(4), 247-259.
http://dx.doi.org/10.1007/BF03353756
[9] Lan, J.; Liu, C.; Gao, M.; Huang, C. An efficient solid-state
synthesis of fluorescent surface carboxylated carbon dots
derived from C60 as a label-free probe for iron ions in liv-
ing cells. Talanta, 2015, 144, 93-97.
http://dx.doi.org/10.1016/j.talanta.2015.05.071 PMID:
26452796
[10] Shen, P.; Xia, Y. Synthesis-modification integration: One-
step fabrication of boronic acid functionalized carbon dots
for fluorescent blood sugar sensing. Anal. Chem., 2014,
86(11), 5323-5329.
http://dx.doi.org/10.1021/ac5001338 PMID: 24694081
[11] Zhang, X.; Wei, C.; Li, Y.; Yu, D. Shining luminescent
graphene quantum dots: Synthesis, physicochemical proper-
ties, and biomedical applications. Trends Analyt. Chem.,
2019, 116, 109-121.
http://dx.doi.org/10.1016/j.trac.2019.03.011
[12] Zhang, X.; Jiang, M.; Niu, N.; Chen, Z.; Li, S.; Liu, S.; Li,
J. Review of natural product derived carbon dots: From
natural products to functional materials. ChemSusChem,
2018, 11(1), 11-24.
http://dx.doi.org/10.1002/cssc.201701847 PMID: 29072348
[13] Niu, W.J.; Li, Y.; Zhu, R.H.; Shan, D.; Fan, Y.R.; Zhang,
X.J. Ethylenediamine-assisted hydrothermal synthesis of ni-
trogen-doped carbon quantum dots as fluorescent probes for
sensitive biosensing and bioimaging. Sens. Actuators B
Chem., 2015, 218, 229-236.
http://dx.doi.org/10.1016/j.snb.2015.05.006
[14] Nair, A.; Haponiuk, J.T.; Thomas, S.; Gopi, S. Natural car-
bon-based quantum dots and their applications in drug de-
livery: A review. Biomed. Pharmacother., 2020, 132,
110834-110849.
http://dx.doi.org/10.1016/j.biopha.2020.110834 PMID:
33035830
[15] Liu, S.; Tian, J.; Wang, L.; Zhang, Y.; Qin, X.; Luo, Y.;
Asiri, A.M.; Al-Youbi, A.O.; Sun, X. Hydrothermal treat-
ment of grass: A low-cost, green route to nitrogen-doped,
carbon-rich, photoluminescent polymer nanodots as an ef-
fective fluorescent sensing platform for label-free detection
of Cu(II) ions. Adv. Mater., 2012, 24(15), 2037-2041.
http://dx.doi.org/10.1002/adma.201200164 PMID:
22419383
[16] Gayen, B.; Palchoudhury, S.; Chowdhury, J. Carbon dots:
A mystic star in the world of nanoscience. J. Nanomater.,
2019, 2019, 1-19.
http://dx.doi.org/10.1155/2019/3451307
[17] Qiao, Z.A.; Wang, Y.; Gao, Y.; Li, H.; Dai, T.; Liu, Y.;
Huo, Q. Commercially activated carbon as the source for
producing multicolor photoluminescent carbon dots by
chemical oxidation. Chem. Commun., 2010, 46(46), 8812-
8814.
http://dx.doi.org/10.1039/c0cc02724c PMID: 20953494
[18] Vinoth Kumar, J.; Kavitha, G.; Arulmozhi, R.; Arul, V.;
Singaravadivel, S.; Abirami, N. Green sources derived car-
bon dots for multifaceted applications. J. Fluoresc., 2021,
31(4), 915-932.
http://dx.doi.org/10.1007/s10895-021-02721-4 PMID:
33786684
[19] Purbia, R.; Paria, S. A simple turn on fluorescent sensor for
the selective detection of thiamine using coconut water de-
rived luminescent carbon dots. Biosens. Bioelectron., 2016,
79, 467-475.
http://dx.doi.org/10.1016/j.bios.2015.12.087 PMID:
26745793
[20] Wang, N.; Wang, Y.; Guo, T.; Yang, T.; Chen, M.; Wang,
J. Green preparation of carbon dots with papaya as carbon
source for effective fluorescent sensing of Iron (III) and
Escherichia coli. Biosens. Bioelectron., 2016, 85, 68-75.
http://dx.doi.org/10.1016/j.bios.2016.04.089 PMID:
27155118
[21] Liao, J.; Cheng, Z.; Zhou, L. Nitrogen-doping enhanced
fluorescent carbon dots: Green synthesis and their applica-
tions for bioimaging and label-free detection of Au3+ ions.
ACS Sustain. Chem. Eng., 2016, 4(6), 3053-3061.
http://dx.doi.org/10.1021/acssuschemeng.6b00018
[22] Arul, V.; Edison, T.N.J.I.; Lee, Y.R.; Sethuraman, M.G.
Biological and catalytic applications of green synthesized
fluorescent N-doped carbon dots using Hylocereus undatus.
J. Photochem. Photobiol. B, 2017, 168, 142-148.
http://dx.doi.org/10.1016/j.jphotobiol.2017.02.007 PMID:
28222361
[23] Arul, V.; Sethuraman, M.G. Facile green synthesis of fluo-
rescent N-doped carbon dots from Actinidia deliciosa and
their catalytic activity and cytotoxicity applications. Opt.
Mater., 2018, 78, 181-190.
http://dx.doi.org/10.1016/j.optmat.2018.02.029
[24] He, M.; Zhang, J.; Wang, H.; Kong, Y.; Xiao, Y.; Xu, W.
Material and optical properties of fluorescent carbon quan-
tum dots fabricated from lemon juice via hydrothermal re-
action. Nanoscale Res. Lett., 2018, 13(1), 175.
http://dx.doi.org/10.1186/s11671-018-2581-7 PMID:
29882047
[25] Ahmadian-Fard-Fini, S.; Salavati-Niasari, M.; Ghanbari, D.
Hydrothermal green synthesis of magnetic Fe3O4-carbon
dots by lemon and grape fruit extracts and as a photolumi-
nescence sensor for detecting of E. coli bacteria. Spectro-
chim. Acta A Mol. Biomol. Spectrosc., 2018, 203, 481-493.
http://dx.doi.org/10.1016/j.saa.2018.06.021 PMID:
29898431
[26] Guo, X.; Zhu, Y.; Zhou, L.; Zhang, L.; You, Y.; Zhang, H.;
Hao, J. A facile and green approach to prepare carbon dots
with pH-dependent fluorescence for patterning and bioim-
aging. RSC Advances, 2018, 8(66), 38091-38099.
http://dx.doi.org/10.1039/C8RA07584K PMID: 35558597
[27] Monte-Filho, S.S.; Andrade, S.I.E.; Lima, M.B.; Araujo,
M.C.U. Synthesis of highly fluorescent carbon dots from
lemon and onion juices for determination of riboflavin in
multivitamin/mineral supplements. J. Pharm. Anal., 2019,
9(3), 209-216.
http://dx.doi.org/10.1016/j.jpha.2019.02.003 PMID:
31297299
[28] Zulfajri, M.; Dayalan, S.; Li, W.Y.; Chang, C.J.; Chang,
Y.P.; Huang, G.G. Nitrogen-doped carbon dots from Aver-
rhoa carambola fruit extract as a fluorescent probe for me-
thyl orange. Sensors, 2019, 19(22), 5008.
http://dx.doi.org/10.3390/s19225008 PMID: 31744145
[29] Desai, M.L.; Jha, S.; Basu, H.; Singhal, R.K.; Park, T.J.;
Kailasa, S.K. Acid oxidation of muskmelon fruit for the
22 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
fabrication of carbon dots with specific emission colours for
recognition of Hg2+ ions and cell imaging. ACS Omega,
2019, 4(21), 19332-19340.
http://dx.doi.org/10.1021/acsomega.9b02730 PMID:
31763557
[30] Dias, C.; Vasimalai, N.; P Sárria, M.; Pinheiro, I.; Vilas-
Boas, V.; Peixoto, J.; Espiña, B. Biocompatibility and bi-
oimaging potential of fruit-based carbon dots. Nanomateri-
als, 2019, 9(2), 199-208.
http://dx.doi.org/10.3390/nano9020199 PMID: 30717497
[31] Atchudan, R.; Jebakumar Immanuel Edison, T.N.; Perumal,
S.; Lee, Y.R. Indian gooseberry-derived tunable fluorescent
carbon dots as a promise for in vitro/in vivo multicolor bi-
oimaging and fluorescent ink. ACS Omega, 2018, 3(12),
17590-17601.
http://dx.doi.org/10.1021/acsomega.8b02463
[32] Ma, H.; Sun, C.; Xue, G.; Wu, G.; Zhang, X.; Han, X.; Qi,
X.; Lv, X.; Sun, H.; Zhang, J. Facile synthesis of fluores-
cent carbon dots from Prunus cerasifera fruits for fluores-
cent ink, Fe3+ ion detection and cell imaging. Spectrochim.
Acta A Mol. Biomol. Spectrosc., 2019, 213, 281-287.
http://dx.doi.org/10.1016/j.saa.2019.01.079 PMID:
30703711
[33] Bhamore, J.R.; Jha, S.; Park, T.J.; Kailasa, S.K. Green syn-
thesis of multi-color emissive carbon dots from Manilkara
zapota fruits for bioimaging of bacterial and fungal cells. J.
Photochem. Photobiol. B, 2019, 191, 150-155.
http://dx.doi.org/10.1016/j.jphotobiol.2018.12.023 PMID:
30639997
[34] Sangubotla, R.; Kim, J. A facile enzymatic approach for
selective detection of γ-aminobutyric acid using corn-
derived fluorescent carbon dots. Appl. Surf. Sci., 2019, 490,
61-69.
http://dx.doi.org/10.1016/j.apsusc.2019.05.320
[35] Gupta, D.A.; Desai, M.L.; Malek, N.I.; Kailasa, S.K. Fluo-
rescence detection of Fe3+ ion using ultra-small fluorescent
carbon dots derived from pineapple (Ananas comosus): De-
velopment of miniaturized analytical method. J. Mol.
Struct., 2020, 1216(1216), 128343.
http://dx.doi.org/10.1016/j.molstruc.2020.128343
[36] Liu, W.; Diao, H.; Chang, H.; Wang, H.; Li, T.; Wei, W.
Green synthesis of carbon dots from rose-heart radish and
application for Fe3+ detection and cell imaging. Sens. Actua-
tors B Chem., 2017, 241, 190-198.
http://dx.doi.org/10.1016/j.snb.2016.10.068
[37] Shen, J.; Shang, S.; Chen, X.; Wang, D.; Cai, Y. Facile
synthesis of fluorescence carbon dots from sweet potato for
Fe3+ sensing and cell imaging. Mater. Sci. Eng. C, 2017, 76,
856-864.
http://dx.doi.org/10.1016/j.msec.2017.03.178 PMID:
28482600
[38] Romero, V.; Vila, V.; de la Calle, I.; Lavilla, I.; Bendicho,
C. Turn–on fluorescent sensor for the detection of periodate
anion following photochemical synthesis of nitrogen and
sulphur co–doped carbon dots from vegetables. Sens. Ac-
tuators B Chem., 2019, 280, 290-297.
http://dx.doi.org/10.1016/j.snb.2018.10.064
[39] Ashrafi Tafreshi, F.; Fatahi, Z.; Ghasemi, S.F.; Taherian,
A.; Esfandiari, N. Ultrasensitive fluorescent detection of
pesticides in real sample by using green carbon dots. PLoS
One, 2020, 15(3), e0230646.
http://dx.doi.org/10.1371/journal.pone.0230646 PMID:
32208468
[40] Hu, Y.; Zhang, L.; Li, X.; Liu, R.; Lin, L.; Zhao, S. Green
preparation of S and N Co-doped carbon dots from water
chestnut and onion as well as their use as an off–on fluores-
cent probe for the quantification and imaging of coenzyme
A. ACS Sustain. Chem. Eng., 2017, 5(6), 4992-5000.
http://dx.doi.org/10.1021/acssuschemeng.7b00393
[41] Lai, Z.; Guo, X.; Cheng, Z.; Ruan, G.; Du, F. Green synthe-
sis of fluorescent carbon dots from cherry tomatoes for
highly effective detection of trifluralin herbicide in soil
samples. ChemistrySelect, 2020, 5(6), 1956-1960.
http://dx.doi.org/10.1002/slct.201904517
[42] Konwar, A.; Deb, A.; Kar, A.; Chowdhury, D. Dual emis-
sion carbon dots from carotenoids: Converting a single
emission to dual emission. Luminescence, 2019, 34(8), 790-
795.
http://dx.doi.org/10.1002/bio.3685 PMID: 31397062
[43] Zhang, Z.; Hu, B.; Zhuang, Q.; Wang, Y.; Luo, X.; Xie, Y.;
Zhou, D. Green synthesis of fluorescent nitrogen–sulfur Co-
doped carbon dots from scallion leaves for hemin sensing.
Anal. Lett., 2020, 53(11), 1704-1718.
http://dx.doi.org/10.1080/00032719.2020.1716782
[44] Tyagi, A.; Tripathi, K.M.; Singh, N.; Choudhary, S.; Gupta,
R.K. Green synthesis of carbon quantum dots from lemon
peel waste: Applications in sensing and photocatalysis. RSC
Advances, 2016, 6(76), 72423-72432.
http://dx.doi.org/10.1039/C6RA10488F
[45] Chatzimitakos, T.; Kasouni, A.; Sygellou, L.; Avgeropou-
los, A.; Troganis, A.; Stalikas, C. Two of a kind but differ-
ent: Luminescent carbon quantum dots from Citrus peels
for iron and tartrazine sensing and cell imaging. Talanta,
2017, 175, 305-312.
http://dx.doi.org/10.1016/j.talanta.2017.07.053 PMID:
28841995
[46] Gudimella, K.K.; Appidi, T.; Wu, H.F.; Battula, V.; Jog-
dand, A.; Rengan, A.K.; Gedda, G. Sand bath assisted green
synthesis of carbon dots from citrus fruit peels for free radi-
cal scavenging and cell imaging. Colloids Surf. B Biointer-
faces, 2021, 197, 111362.
http://dx.doi.org/10.1016/j.colsurfb.2020.111362 PMID:
33038604
[47] Wang, M.; Shi, R.; Gao, M.; Zhang, K.; Deng, L.; Fu, Q.;
Wang, L.; Gao, D. Sensitivity fluorescent switching sensor
for Cr (VI) and ascorbic acid detection based on orange
peels-derived carbon dots modified with EDTA. Food
Chem., 2020, 318, 126506-126517.
http://dx.doi.org/10.1016/j.foodchem.2020.126506 PMID:
32126473
[48] Vandarkuzhali, S.A.A.; Natarajan, S.; Jeyabalan, S.; Siva-
raman, G.; Singaravadivel, S.; Muthusubramanian, S.;
Viswanathan, B. Pineapple peel-derived carbon dots: Ap-
plications as sensor, molecular keypad lock, and memory
device. ACS Omega, 2018, 3(10), 12584-12592.
http://dx.doi.org/10.1021/acsomega.8b01146 PMID:
30411011
[49] Atchudan, R.; Edison, T.N.J.I.; Perumal, S.; Muthuchamy,
N.; Lee, Y.R. Hydrophilic nitrogen-doped carbon dots from
biowaste using dwarf banana peel for environmental and
biological applications. Fuel, 2020, 275, 117821-117831.
http://dx.doi.org/10.1016/j.fuel.2020.117821
[50] Muktha, H.; Sharath, R.; Kottam, N.; Smrithi, S.P.; Samrat,
K.; Ankitha, P. Green synthesis of carbon dots and evalua-
tion of its pharmacological activities. Bionanoscience,
2020, 10(3), 731-744.
http://dx.doi.org/10.1007/s12668-020-00741-1
[51] Jiao, X.Y.; Li, L.S.; Qin, S.; Zhang, Y.; Huang, K.; Xu, L.
The synthesis of fluorescent carbon dots from mango peel
and their multiple applications. Colloids Surf. A Physico-
chem. Eng., 2019, 577, 306-314.
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 23
[52] Sahoo, N.K.; Jana, G.C.; Aktara, M.N.; Das, S.; Nayim, S.;
Patra, A.; Bhattacharjee, P.; Bhadra, K.; Hossain, M. Car-
bon dots derived from lychee waste: Application for Fe3+
ions sensing in real water and multicolor cell imaging of
skin melanoma cells. Mater. Sci. Eng. C, 2020, 108,
110429.
http://dx.doi.org/10.1016/j.msec.2019.110429 PMID:
31923934
[53] Liu, H.; Ding, L.; Chen, L.; Chen, Y.; Zhou, T.; Li, H.; Xu,
Y.; Zhao, L.; Huang, N. A facile, green synthesis of bio-
mass carbon dots coupled with molecularly imprinted pol-
ymers for highly selective detection of oxytetracycline. J.
Ind. Eng. Chem., 2019, 69, 455-463.
http://dx.doi.org/10.1016/j.jiec.2018.10.007
[54] Jayaweera, S.; Yin, K.; Ng, W.J. Nitrogen-doped durian
shell derived carbon dots for inner filter effect mediated
sensing of tetracycline and fluorescent ink. J. Fluoresc.,
2019, 29(1), 221-229.
http://dx.doi.org/10.1007/s10895-018-2331-3 PMID:
30565002
[55] Amin, N.; Afkhami, A.; Hosseinzadeh, L.; Madrakian, T.
Green and cost-effective synthesis of carbon dots from date
kernel and their application as a novel switchable fluores-
cence probe for sensitive assay of Zoledronic acid drug in
human serum and cellular imaging. Anal. Chim. Acta, 2018,
1030, 183-193.
http://dx.doi.org/10.1016/j.aca.2018.05.014 PMID:
30032768
[56] Chandra, S.; Singh, V.K.; Yadav, P.K.; Bano, D.; Kumar,
V.; Pandey, V.K.; Talat, M.; Hasan, S.H. Mustard seeds de-
rived fluorescent carbon quantum dots and their peroxidase-
like activity for colorimetric detection of H2O2 and ascorbic
acid in a real sample. Anal. Chim. Acta, 2019, 1054, 145-
156.
http://dx.doi.org/10.1016/j.aca.2018.12.024 PMID:
30712585
[57] Raji, K.; Ramanan, V.; Ramamurthy, P. Facile and green
synthesis of highly fluorescent nitrogen-doped carbon dots
from jackfruit seeds and its applications towards the fluori-
metric detection of Au3+ ions in aqueous medium and in in
vitro multicolor cell imaging. New J. Chem., 2019, 43(29),
11710-11719.
http://dx.doi.org/10.1039/C9NJ02590A
[58] v, R.; Misra, S.; Santra, M.K.; Ottoor, D. One pot green
synthesis of C-dots from groundnuts and its application as
Cr(VI) sensor and in vitro bioimaging agent. J. Photochem.
Photobiol. Chem., 2019, 373, 28-36.
http://dx.doi.org/10.1016/j.jphotochem.2018.12.028
[59] Li, K.; Xu, J.; Arsalan, M.; Cheng, N.; Sheng, Q.; Zheng, J.;
Cao, W.; Yue, T. Nitrogen doped carbon dots derived from
natural seeds and their application for electrochemical sens-
ing. J. Electrochem. Soc., 2019, 166(2), B56-B62.
http://dx.doi.org/10.1149/2.0501902jes
[60] Vasimalai, N.; Vilas-Boas, V.; Gallo, J.; Cerqueira, M.F.;
Menéndez-Miranda, M.; Costa-Fernández, J.M.; Diéguez,
L.; Espiña, B.; Fernández-Argüelles, M.T. Green synthesis
of fluorescent carbon dots from spices for in vitro imaging
and tumour cell growth inhibition. Beilstein J. Nanotech-
nol., 2018, 9(1), 530-544.
http://dx.doi.org/10.3762/bjnano.9.51 PMID: 29527430
[61] Long, R.; Guo, Y.; Xie, L.; Shi, S.; Xu, J.; Tong, C.; Lin,
Q.; Li, T. White pepper-derived ratiometric carbon dots for
highly selective detection and imaging of coenzyme A.
Food Chem., 2020, 315, 126171-126177.
http://dx.doi.org/10.1016/j.foodchem.2020.126171 PMID:
31991253
[62] Shahshahanipour, M.; Rezaei, B.; Ensafi, A.A.; Etemadifar,
Z. An ancient plant for the synthesis of a novel carbon dot
and its applications as an antibacterial agent and probe for
sensing of an anti-cancer drug. Mater. Sci. Eng. C, 2019,
98, 826-833.
http://dx.doi.org/10.1016/j.msec.2019.01.041 PMID:
30813088
[63] Prathumsuwan, T.; Jaiyong, P.; In, I.; Paoprasert, P. Label-
free carbon dots from water hyacinth leaves as a highly flu-
orescent probe for selective and sensitive detection of bo-
rax. Sens. Actuators B Chem., 2019, 299, 126936-126947.
http://dx.doi.org/10.1016/j.snb.2019.126936
[64] Jiang, X.; Qin, D.; Mo, G.; Feng, J.; Yu, C.; Mo, W.; Deng,
B. Ginkgo leaf-based synthesis of nitrogen-doped carbon
quantum dots for highly sensitive detection of salazosulfa-
pyridine in mouse plasma. J. Pharm. Biomed. Anal., 2019,
164, 514-519.
http://dx.doi.org/10.1016/j.jpba.2018.11.025 PMID:
30453158
[65] Raveendran, V.; Suresh Babu, A.R.; Renuka, N.K. Mint
leaf derived carbon dots for dual analyte detection of Fe(III)
and ascorbic acid. RSC Advances, 2019, 9(21), 12070-
12077.
http://dx.doi.org/10.1039/C9RA02120E PMID: 35517017
[66] Yadav, P.K.; Singh, V.K.; Chandra, S.; Bano, D.; Kumar,
V.; Talat, M.; Hasan, S.H. Green synthesis of fluorescent
carbon quantum dots from Azadirachta indica leaves and
their peroxidase-mimetic activity for the detection of H2O2
and ascorbic acid in common fresh fruits. ACS Biomater.
Sci. Eng., 2019, 5(2), 623-632.
http://dx.doi.org/10.1021/acsbiomaterials.8b01528 PMID:
33405826
[67] Deb, A.; Saikia, R.; Chowdhury, D. Nano-Bioconjugate
film from Aloe vera to detect hazardous chemicals used in
cosmetics. ACS Omega, 2019, 4(23), 20394-20401.
http://dx.doi.org/10.1021/acsomega.9b03280 PMID:
31815243
[68] Ran, Y.; Wang, S.; Yin, Q.; Wen, A.; Peng, X.; Long, Y.;
Chen, S. Green synthesis of fluorescent carbon dots using
chloroplast dispersions as precursors and application for
Fe3+ ion sensing. Luminescence, 2020, 35(6), 870-876.
http://dx.doi.org/10.1002/bio.3794 PMID: 32142218
[69] Zhang, Y.P.; Ma, J.M.; Yang, Y.S.; Ru, J.X.; Liu, X.Y.;
Ma, Y.; Guo, H.C. Synthesis of nitrogen-doped graphene
quantum dots (N-GQDs) from marigold for detection of
Fe3+ ion and bioimaging. Spectrochim. Acta A Mol. Biomol.
Spectrosc., 2019, 217, 60-67.
http://dx.doi.org/10.1016/j.saa.2019.03.044 PMID:
30927572
[70] Ensafi, A.A.; Hghighat Sefat, S.; Kazemifard, N.; Rezaei,
B.; Moradi, F. A novel one-step and green synthesis of
highly fluorescent carbon dots from saffron for cell imaging
and sensing of prilocaine. Sens. Actuators B Chem., 2017,
253, 451-460.
http://dx.doi.org/10.1016/j.snb.2017.06.163
[71] Huang, Q.; Li, Q.; Chen, Y.; Tong, L.; Lin, X.; Zhu, J.;
Tong, Q. High quantum yield nitrogen-doped carbon dots:
Green synthesis and application as “off-on” fluorescent sen-
sors for the determination of Fe3+ and adenosine triphos-
phate in biological samples. Sens. Actuators B Chem., 2018,
276, 82-88.
http://dx.doi.org/10.1016/j.snb.2018.08.089
[72] Shukla, D.; Pandey, F.P.; Kumari, P.; Basu, N.; Tiwari,
M.K.; Lahiri, J.; Kharwar, R.N.; Parmar, A.S. Label-free
fluorometric detection of adulterant malachite green using
24 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
carbon dots derived from the medicinal plant source Oci-
mum tenuiflorum. ChemistrySelect, 2019, 4(17), 4839-4847.
http://dx.doi.org/10.1002/slct.201900530
[73] Naik, G.G.; Alam, M.B.; Pandey, V.; Mohapatra, D.;
Dubey, P.K.; Parmar, A.S.; Sahu, A.N. Multi-functional
carbon dots from an ayurvedic medicinal plant for cancer
cell bioimaging applications. J. Fluoresc., 2020, 30(2), 407-
418.
http://dx.doi.org/10.1007/s10895-020-02515-0 PMID:
32088852
[74] Guo, Y.; Zhang, L.; Cao, F.; Leng, Y. Thermal treatment of
hair for the synthesis of sustainable carbon quantum dots
and the applications for sensing Hg2+. Sci. Rep., 2016, 6(1),
35795.
http://dx.doi.org/10.1038/srep35795 PMID: 27762342
[75] Chatzimitakos, T.; Kasouni, A.; Sygellou, L.; Leonardos, I.;
Troganis, A.; Stalikas, C. Human fingernails as an intri-
guing precursor for the synthesis of nitrogen and sulfur-
doped carbon dots with strong fluorescent properties: Ana-
lytical and bioimaging applications. Sens. Actuators B
Chem., 2018, 267, 494-501.
http://dx.doi.org/10.1016/j.snb.2018.04.059
[76] Hua, X.W.; Bao, Y.W.; Wang, H.Y.; Chen, Z.; Wu, F.G.
Bacteria-derived fluorescent carbon dots for microbial
live/dead differentiation. Nanoscale, 2017, 9(6), 2150-2161.
http://dx.doi.org/10.1039/C6NR06558A PMID: 27874123
[77] Lin, F.; Li, C.; Dong, L.; Fu, D.; Chen, Z. Imaging biofilm-
encased microorganisms using carbon dots derived from L.
plantarum. Nanoscale, 2017, 9(26), 9056-9064.
http://dx.doi.org/10.1039/C7NR01975K PMID: 28639672
[78] Zhang, S.; Zhang, D.; Ding, Y.; Hua, J.; Tang, B.; Ji, X.;
Zhang, Q.; Wei, Y.; Qin, K.; Li, B. Bacteria-derived fluo-
rescent carbon dots for highly selective detection of p-
nitrophenol and bioimaging. Analyst, 2019, 144(18), 5497-
5503.
http://dx.doi.org/10.1039/C9AN01103J PMID: 31386712
[79] Yu, Y.; Li, C.; Chen, C.; Huang, H.; Liang, C.; Lou, Y.;
Chen, X.B.; Shi, Z.; Feng, S. Saccharomyces-derived car-
bon dots for biosensing pH and vitamin B 12. Talanta,
2019, 195, 117-126.
http://dx.doi.org/10.1016/j.talanta.2018.11.010 PMID:
30625521
[80] Singh, A.K.; Singh, V.K.; Singh, M.; Singh, P.; Khadim,
S.R.; Singh, U.; Koch, B.; Hasan, S.H.; Asthana, R.K. One
pot hydrothermal synthesis of fluorescent NP-carbon dots
derived from Dunaliella salina biomass and its application
in on-off sensing of Hg (II), Cr (VI) and live cell imaging.
J. Photochem. Photobiol. Chem., 2019, 376, 63-72.
http://dx.doi.org/10.1016/j.jphotochem.2019.02.023
[81] Bandi, R.; Gangapuram, B.R.; Dadigala, R.; Eslavath, R.;
Singh, S.S.; Guttena, V. Facile and green synthesis of fluo-
rescent carbon dots from onion waste and their potential
applications as sensor and multicolour imaging agents. RSC
Advances, 2016, 6(34), 28633-28639.
http://dx.doi.org/10.1039/C6RA01669C
[82] Feng, J.; Wang, W.J.; Hai, X.; Yu, Y.L.; Wang, J.H. Green
preparation of nitrogen-doped carbon dots derived from
silkworm chrysalis for cell imaging. J. Mater. Chem. B Ma-
ter. Biol. Med., 2016, 4(3), 387-393.
http://dx.doi.org/10.1039/C5TB01999K PMID: 32263205
[83] Yao, Y.Y.; Gedda, G.; Girma, W.M.; Yen, C.L.; Ling,
Y.C.; Chang, J.Y. Magnetofluorescent carbon dots derived
from crab shell for targeted dual-modality bioimaging and
drug delivery. ACS Appl. Mater. Interfaces, 2017, 9(16),
13887-13899.
http://dx.doi.org/10.1021/acsami.7b01599 PMID: 28388048
[84] Huang, G.; Chen, X.; Wang, C.; Zheng, H.; Huang, Z.;
Chen, D.; Xie, H. Photoluminescent carbon dots derived
from sugarcane molasses: Synthesis, properties, and appli-
cations. RSC Advances, 2017, 7(75), 47840-47847.
http://dx.doi.org/10.1039/C7RA09002A
[85] Thongsai, N.; Tanawannapong, N.; Praneerad, J.; Kladsom-
boon, S.; Jaiyong, P.; Paoprasert, P. Real-time detection of
alcohol vapors and volatile organic compounds via optical
electronic nose using carbon dots prepared from rice husk
and density functional theory calculation. Colloids Surf. A
Physicochem. Eng. Asp., 2019, 560, 278-287.
http://dx.doi.org/10.1016/j.colsurfa.2018.09.077
[86] Picard, M.; Thakur, S.; Misra, M.; Mohanty, A.K. Miscan-
thus grass-derived carbon dots to selectively detect Fe3+
ions. RSC Advances, 2019, 9(15), 8628-8637.
http://dx.doi.org/10.1039/C8RA10051A PMID: 35518702
[87] Deb, A.; Konwar, A.; Chowdhury, D. pH-responsive hybrid
jute carbon dot-cotton patch. ACS Sustain. Chem. Eng.,
2020, 8(19), 7394-7402.
http://dx.doi.org/10.1021/acssuschemeng.0c01221
[88] Pramanik, S.; Chatterjee, S.; Suresh Kumar, G.; Sujatha
Devi, P. Egg-shell derived carbon dots for base pair selec-
tive DNA binding and recognition. Phys. Chem. Chem.
Phys., 2018, 20(31), 20476-20488.
http://dx.doi.org/10.1039/C8CP02872A PMID: 30043811
[89] Venkatesan, G.; Rajagopalan, V.; Chakravarthula, S.N.
Boswellia ovalifoliolata bark extract derived carbon dots for
selective fluorescent sensing of Fe3+. J. Environ. Chem.
Eng., 2019, 7(2), 103013.
http://dx.doi.org/10.1016/j.jece.2019.103013
[90] Tiwari, P.; Kaur, N.; Sharma, V.; Kang, H.; Uddin, J.; Mo-
bin, S.M. Cannabis sativa -derived carbon dots co-doped
with N–S: Highly efficient nanosensors for temperature and
vitamin B12. New J. Chem., 2019, 43(43), 17058-17068.
http://dx.doi.org/10.1039/C9NJ04061G
[91] Zulfajri, M.; Gedda, G.; Chang, C.J.; Chang, Y.P.; Huang,
G.G. Cranberry beans derived carbon dots as a potential
fluorescence sensor for selective detection of Fe3+ ions in
aqueous solution. ACS Omega, 2019, 4(13), 15382-15392.
http://dx.doi.org/10.1021/acsomega.9b01333 PMID:
31572837
[92] Wei, X.; Li, L.; Liu, J.; Yu, L.; Li, H.; Cheng, F.; Yi, X.;
He, J.; Li, B. Green synthesis of fluorescent carbon dots
from gynostemma for bioimaging and antioxidant in
zebrafish. ACS Appl. Mater. Interfaces, 2019, 11(10), 9832-
9840.
http://dx.doi.org/10.1021/acsami.9b00074 PMID: 30758177
[93] Chen, K.; Qing, W.; Hu, W.; Lu, M.; Wang, Y.; Liu, X. On-
off-on fluorescent carbon dots from waste tea: Their proper-
ties, antioxidant and selective detection of CrO4
2−, Fe3+,
ascorbic acid and L-cysteine in real samples. Spectrochim.
Acta A Mol. Biomol. Spectrosc., 2019, 213, 228-234.
http://dx.doi.org/10.1016/j.saa.2019.01.066 PMID:
30695741
[94] Shukla, D.; Das, M.; Kasade, D.; Pandey, M.; Dubey, A.K.;
Yadav, S.K.; Parmar, A.S. Sandalwood-derived carbon
quantum dots as bioimaging tools to investigate the toxico-
logical effects of malachite green in model organisms.
Chemosphere, 2020, 248, 125998.
http://dx.doi.org/10.1016/j.chemosphere.2020.125998
PMID: 32006833
[95] Newman Monday, Y.; Abdullah, J.; Yusof, N.A.; Abdul
Rashid, S.; Shueb, R.H. Facile hydrothermal and sol-
vothermal synthesis and characterization of nitrogen-doped
carbon dots from palm kernel shell precursor. Appl. Sci.,
2021, 11(4), 1630.
Biogenic Carbon Quantum Dots: Synthesis and Applications Current Medicinal Chemistry, XXXX, Vol. XX, No. XX 25
http://dx.doi.org/10.3390/app11041630
[96] Huang, C.; Dong, H.; Su, Y.; Wu, Y.; Narron, R.; Yong, Q.
Synthesis of carbon quantum dot nanoparticles derived
from byproducts in bio-refinery process for cell imaging
and in vivo bioimaging. Nanomaterials, 2019, 9(3), 387.
http://dx.doi.org/10.3390/nano9030387 PMID: 30866423
[97] Zhu, S.; Song, Y.; Zhao, X.; Shao, J.; Zhang, J.; Yang, B.
The photoluminescence mechanism in carbon dots (gra-
phene quantum dots, carbon nanodots, and polymer dots):
Current state and future perspective. Nano Res., 2015, 8(2),
355-381.
http://dx.doi.org/10.1007/s12274-014-0644-3
[98] Liu, M.L.; Chen, B.B.; Li, C.M.; Huang, C.Z. Carbon dots:
Synthesis, formation mechanism, fluorescence origin and
sensing applications. Green Chem., 2019, 21(3), 449-471.
http://dx.doi.org/10.1039/C8GC02736F
[99] Jiang, K.; Sun, S.; Zhang, L.; Lu, Y.; Wu, A.; Cai, C.; Lin,
H. Red, green, and blue luminescence by carbon dots: Full-
color emission tuning and multicolor cellular imaging. An-
gew. Chem. Int. Ed., 2015, 54(18), 5360-5363.
http://dx.doi.org/10.1002/anie.201501193 PMID: 25832292
[100] Li, H.; He, X.; Kang, Z.; Huang, H.; Liu, Y.; Liu, J.; Lian,
S.; Tsang, C.H.A.; Yang, X.; Lee, S.T. Water-soluble fluo-
rescent carbon quantum dots and photocatalyst design. An-
gew. Chem. Int. Ed., 2010, 49(26), 4430-4434.
http://dx.doi.org/10.1002/anie.200906154 PMID: 20461744
[101] Zhang, Y.; Yuan, R.; He, M.; Hu, G.; Jiang, J.; Xu, T.;
Zhou, L.; Chen, W.; Xiang, W.; Liang, X. Multicolour ni-
trogen-doped carbon dots: Tunable photoluminescence and
sandwich fluorescent glass-based light-emitting diodes. Na-
noscale, 2017, 9(45), 17849-17858.
http://dx.doi.org/10.1039/C7NR05363K PMID: 29116274
[102] Ding, H.; Yu, S.B.; Wei, J.S.; Xiong, H.M. Full-color light-
emitting carbon dots with a surface-state-controlled lumi-
nescence mechanism. ACS Nano, 2016, 10(1), 484-491.
http://dx.doi.org/10.1021/acsnano.5b05406 PMID:
26646584
[103] Guo, Y.; Wang, Z.; Shao, H.; Jiang, X. Hydrothermal syn-
thesis of highly fluorescent carbon nanoparticles from sodi-
um citrate and their use for the detection of mercury ions.
Carbon, 2013, 52, 583-589.
http://dx.doi.org/10.1016/j.carbon.2012.10.028
[104] Shibata, K.; Nakai, T.; Fukuwatari, T. Simultaneous high-
performance liquid chromatography determination of coen-
zyme A, dephospho-coenzyme A, and acetyl-coenzyme A
in normal and pantothenic acid-deficient rats. Anal. Bio-
chem., 2012, 430(2), 151-155.
http://dx.doi.org/10.1016/j.ab.2012.08.010 PMID:
22922385
[105] Miller, A.; Korem, M.; Almog, R.; Galboiz, Y. Vitamin
B12, demyelination, remyelination and repair in multiple
sclerosis. J. Neurol. Sci., 2005, 233(1-2), 93-97.
http://dx.doi.org/10.1016/j.jns.2005.03.009 PMID:
15896807
[106] Sun, X.Y.; Yuan, M.J.; Liu, B.; Shen, J.S. Carbon dots as
fluorescent probes for detection of VB12 based on the inner
filter effect. RSC Advances, 2018, 8(35), 19786-19790.
http://dx.doi.org/10.1039/C8RA03070G PMID: 35540996
[107] Ding, L.; Yang, H.; Ge, S.; Yu, J. Fluorescent carbon dots
nanosensor for label-free determination of vitamin B12
based on inner filter effect. Spectrochim. Acta A Mol. Bio-
mol. Spectrosc., 2018, 193, 305-309.
http://dx.doi.org/10.1016/j.saa.2017.12.015 PMID:
29258025
[108] Cho, I.H.; Kim, D.H.; Park, S. Electrochemical biosensors:
Perspective on functional nanomaterials for on-site analysis.
Biomater. Res., 2020, 24(1), 6.
http://dx.doi.org/10.1186/s40824-019-0181-y PMID:
32042441
[109] Farzin, M.A.; Abdoos, H. A critical review on quantum
dots: From synthesis toward applications in electrochemical
biosensors for determination of disease-related biomole-
cules. Talanta, 2021, 224, 121828.
http://dx.doi.org/10.1016/j.talanta.2020.121828 PMID:
33379046
[110] Ji, C.; Zhou, Y.; Leblanc, R.M.; Peng, Z. Recent develop-
ments of carbon dots in biosensing: A review. ACS Sens.,
2020, 5(9), 2724-2741.
http://dx.doi.org/10.1021/acssensors.0c01556 PMID:
32812427
[111] Speed, N.K.; Matthies, H.J.G.; Kennedy, J.P.; Vaughan,
R.A.; Javitch, J.A.; Russo, S.J.; Lindsley, C.W.; Niswender,
K.; Galli, A. Akt-dependent and isoform-specific regulation
of dopamine transporter cell surface expression. ACS Chem.
Neurosci., 2010, 1(7), 476-481.
http://dx.doi.org/10.1021/cn100031t PMID: 22778840
[112] Zhou, J.; Wang, W.; Yu, P.; Xiong, E.; Zhang, X.; Chen, J.
A simple label-free electrochemical aptasensor for dopa-
mine detection. RSC Advances, 2014, 4(94), 52250-52255.
http://dx.doi.org/10.1039/C4RA08090D
[113] Wang, X.; You, Z.; Sha, H.; Cheng, Y.; Zhu, H.; Sun, W.
Sensitive electrochemical detection of dopamine with a
DNA/graphene bi-layer modified carbon ionic liquid elec-
trode. Talanta, 2014, 128, 373-378.
http://dx.doi.org/10.1016/j.talanta.2014.04.078 PMID:
25059174
[114] Jiang, G.; Jiang, T.; Zhou, H.; Yao, J.; Kong, X. Preparation
of N-doped carbon quantum dots for highly sensitive detec-
tion of dopamine by an electrochemical method. RSC Ad-
vances, 2015, 5(12), 9064-9068.
http://dx.doi.org/10.1039/C4RA16773B
[115] Asad, M.; Zulfiqar, A.; Raza, R.; Yang, M.; Hayat, A.;
Akhtar, N. Orange peel derived C-dots decorated CuO na-
norods for the selective monitoring of dopamine from
deboned chicken. Electroanalysis, 2020, 32(1), 11-18.
http://dx.doi.org/10.1002/elan.201900468
[116] Huang, Q.; Lin, X.; Zhu, J.J.; Tong, Q.X. Pd-Au@carbon
dots nanocomposite: Facile synthesis and application as an
ultrasensitive electrochemical biosensor for determination
of colitoxin DNA in human serum. Biosens. Bioelectron.,
2017, 94, 507-512.
http://dx.doi.org/10.1016/j.bios.2017.03.048 PMID:
28343103
[117] Ghodsi, J.; Rafati, A.A.; Shoja, Y. First report on electro-
catalytic oxidation of oxytetracycline by horse radish perox-
idase: Application in developing a biosensor to oxytetracy-
cline determination. Sens. Actuators B Chem., 2016, 224,
692-699.
http://dx.doi.org/10.1016/j.snb.2015.10.091
[118] Johari-Ahar, M.; Barar, J.; Alizadeh, A.M.; Davaran, S.;
Omidi, Y.; Rashidi, M.R. Methotrexate-conjugated quan-
tum dots: Synthesis, characterisation and cytotoxicity in
drug resistant cancer cells. J. Drug Target., 2016, 24(2),
120-133.
http://dx.doi.org/10.3109/1061186X.2015.1058801 PMID:
26176269
[119] Olivieri, A.C.; Arancibia, J.A.; Muñoz de la Peña, A.; Du-
rán-Merás, I.; Espinosa Mansilla, A. Second-order ad-
vantage achieved with four-way fluorescence excitation-
emission-kinetic data processed by parallel factor analysis
26 Current Medicinal Chemistry, XXXX, Vol. XX, No. XX Deb and Chowdhury
and trilinear least-squares. Determination of methotrexate
and leucovorin in human urine. Anal. Chem., 2004, 76(19),
5657-5666.
http://dx.doi.org/10.1021/ac0493065 PMID: 15456283
[120] Nudelman, J.; Taylor, B.; Evans, N.; Rizzo, J.; Gray, J.;
Engel, C.; Walker, M. Policy and research recommenda-
tions emerging from the scientific evidence connecting en-
vironmental factors and breast cancer. Int. J. Occup. Envi-
ron. Health, 2009, 15(1), 79-101.
http://dx.doi.org/10.1179/oeh.2009.15.1.79 PMID:
19267127
[121] Atchudan, R.; Jebakumar Immanuel Edison, T.N.; Shanmu-
gam, M.; Perumal, S.; Somanathan, T.; Lee, Y.R. Sustaina-
ble synthesis of carbon quantum dots from banana peel
waste using hydrothermal process for in vivo bioimaging.
Physica E, 2021, 126, 114417.
http://dx.doi.org/10.1016/j.physe.2020.114417
[122] Qin, K.; Zhang, D.; Ding, Y.; Zheng, X.; Xiang, Y.; Hua, J.;
Zhang, Q.; Ji, X.; Li, B.; Wei, Y. Applications of hydro-
thermal synthesis of Escherichia coli derived carbon dots in
in vitro and in vivo imaging and p -nitrophenol detection.
Analyst, 2020, 145(1), 177-183.
http://dx.doi.org/10.1039/C9AN01753D PMID: 31729506
[123] Xue, M.; Zhao, J.; Zhan, Z.; Zhao, S.; Lan, C.; Ye, F.;
Liang, H. Dual functionalized natural biomass carbon dots
from lychee exocarp for cancer cell targetable near-infrared
fluorescence imaging and photodynamic therapy. Na-
noscale, 2018, 10(38), 18124-18130.
http://dx.doi.org/10.1039/C8NR05017A PMID: 30255925
[124] Esim, O.; Kurbanoglu, S.; Savaser, A.; Ozkan, S.A.; Ozkan,
Y. Nanomaterials for drug delivery systems. New develop-
ments in nanosensors for pharmaceutical analysis; Aca-
demic Press, 2019, pp. 273-301.
http://dx.doi.org/10.1016/B978-0-12-816144-9.00009-2
[125] Koutsogiannis, P.; Thomou, E.; Stamatis, H.; Gournis, D.;
Rudolf, P. Advances in fluorescent carbon dots for biomed-
ical applications. Adv. Phys. X, 2020, 5(1), 1758592.
http://dx.doi.org/10.1080/23746149.2020.1758592
[126] Fahmi, M.Z.; Haris, A.; Permana, A.J.; Nor Wibowo, D.L.;
Purwanto, B.; Nikmah, Y.L.; Idris, A. Bamboo leaf-based
carbon dots for efficient tumor imaging and therapy. RSC
Advances, 2018, 8(67), 38376-38383.
http://dx.doi.org/10.1039/C8RA07944G PMID: 35559085
[127] Liang, L.; Liu, Z. A self-assembled molecular team of bo-
ronic acids at the gold surface for specific capture of cis-
diol biomolecules at neutral pH. Chem. Commun., 2011,
47(8), 2255-2257.
http://dx.doi.org/10.1039/c0cc02540b PMID: 21258740
[128] D’souza, S.L.; Chettiar, S.S.; Koduru, J.R.; Kailasa, S.K.
Synthesis of fluorescent carbon dots using Daucus carota
subsp. sativus roots for mitomycin drug delivery. Optik,
2018, 158, 893-900.
http://dx.doi.org/10.1016/j.ijleo.2017.12.200
[129] Shao, Y.; Zhu, C.; Fu, Z.; Lin, K.; Wang, Y.; Chang, Y.;
Han, L.; Yu, H.; Tian, F. Green synthesis of multifunctional
fluorescent carbon dots from mulberry leaves (Morus alba
L.) residues for simultaneous intracellular imaging and drug
delivery. J. Nanopart. Res., 2020, 22(8), 229.
http://dx.doi.org/10.1007/s11051-020-04917-4
[130] Ankireddy, S.R.; Vo, V.G.; An, S.S.A.; Kim, J. Solvent-
free synthesis of fluorescent carbon dots: An ecofriendly
approach for the bioimaging and screening of anticancer ac-
tivity via caspase-induced apoptosis. ACS Appl. Bio Mater.,
2020, 3(8), 4873-4882.
http://dx.doi.org/10.1021/acsabm.0c00377 PMID:
35021731
[131] Zhu, C.; Zhai, J.; Dong, S. Bifunctional fluorescent carbon
nanodots: Green synthesis via soy milk and application as
metal-free electrocatalysts for oxygen reduction. Chem.
Commun., 2012, 48(75), 9367-9369.
http://dx.doi.org/10.1039/c2cc33844k PMID: 22911246
[132] Zhang, H.; Wang, Y.; Wang, D.; Li, Y.; Liu, X.; Liu, P.;
Yang, H.; An, T.; Tang, Z.; Zhao, H. Hydrothermal trans-
formation of dried grass into graphitic carbon-based high
performance electrocatalyst for oxygen reduction reaction.
Small, 2014, 10(16), 3371-3378.
http://dx.doi.org/10.1002/smll.201400781 PMID: 24729520
[133] Liu, R.; Zhang, H.; Liu, S.; Zhang, X.; Wu, T.; Ge, X.;
Zang, Y.; Zhao, H.; Wang, G. Shrimp-shell derived carbon
nanodots as carbon and nitrogen sources to fabricate three-
dimensional N-doped porous carbon electrocatalysts for the
oxygen reduction reaction. Phys. Chem. Chem. Phys., 2016,
18(5), 4095-4101.
http://dx.doi.org/10.1039/C5CP06970J PMID: 26778836
[134] Li, X.; Rui, M.; Song, J.; Shen, Z.; Zeng, H. Carbon and
graphene quantum dots for optoelectronic and energy de-
vices: A review. Adv. Funct. Mater., 2015, 25(31), 4929-
4947.
http://dx.doi.org/10.1002/adfm.201501250
[135] Unnikrishnan, B.; Wu, C.W.; Chen, I.W.P.; Chang, H.T.;
Lin, C.H.; Huang, C.C. Carbon dot-mediated synthesis of
manganese oxide decorated graphene nanosheets for super-
capacitor application. ACS Sustain. Chem.& Eng., 2016,
4(6), 3008-3016.
http://dx.doi.org/10.1021/acssuschemeng.5b01700
[136] Xu, L.; Wang, H.; Gao, J.; Jin, X. Electrochemical perfor-
mance enhancement of flexible graphene supercapacitor
electrodes by carbon dots modification and NiCo2S4 elec-
trodeposition. J. Alloys Compd., 2019, 809, 151802.
http://dx.doi.org/10.1016/j.jallcom.2019.151802
[137] Li, W.; Liu, Y.; Wu, M.; Feng, X.; Redfern, S. A.; Shang,
Y.; Yang, B. Carbon-quantum-dots-loaded ruthenium na-
noparticles as an efficient electrocatalyst for hydrogen pro-
duction in alkaline media. Adv. Mater., 2018, 30(31),
1800676.
https://doi.org/10.1002/adma.201800676
[138] Unnikrishnan, B.; Wu, C. W.; Chen, I. W. P.; Chang, H. T.;
Lin, C. H.; Huang, C. C. Carbon dot-mediated synthesis of
manganese oxide decorated graphene nanosheets for super-
capacitor application. ACS Sustain. Chem. Eng., 2016, 4(6),
3008-3016.
[139] Xu, L.; Wang, H.; Gao, J.; Jin, X. Electrochemical perfor-
mance enhancement of flexible graphene supercapacitor
electrodes by carbon dots modification and NiCo 2 S 4 elec-
trodeposition. J. Alloys Compd., 2019, 809, 151802.
[140] Hoang, V. C.; Nguyen, L. H.; Gomes, V. G. High efficiency
supercapacitor derived from biomass based carbon dots and
reduced graphene oxide composite. J. Electroanal. Chem.,
2019, 832, 87?96.
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