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Anti-glycation Effect of Gold Nanoparticles on Collagen


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Gold nanoparticles (GNPs) have been reported to exhibit a variety of biological effects including anti-inflammatory and anti-oxidant activities. The extent of an in vitro glycation reaction mixture of collagen and glycolaldehyde was assayed to investigate the inhibition of glycolaldehye-derived advanced glycation end products (glycol-AGEs) formation with GNPs in collagen, which is a major protein component of the human dermis. GNP-treated collagen showed significantly less glycation (56.3 ± 4.2%) than an untreated glycation control. Moreover, GNP-treated glycation in a collagen lattice model significantly decreased the AGEs distribution in the model system. Taken together, these results suggest that GNPs have the potential for use in the prevention of glycation-induced skin aging.
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260 Vol. 35, No. 2
© 2012 The Pha rmaceutical Society of Japan
Biol. Pharm. Bull. 35(2) 260264 (2012)
Anti-glycation Effect of Gold Nanoparticles on Collagen
Ji-hoon Kim,a,# Chung-Oui Hong,a,# Yun-chang Koo,a Hee-Don Choi,b and Kwang-Won Lee*,a
a Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University; Seoul
136–701, Republic of Korea: and b Korea Food Research Institue; Baekhyun-dong, Bundang-ku, Sungnam, Gyeonggi-
do 463–746, Republic of Korea.
Received August 25, 2011; accepted November 21, 2011; published online November 25, 2011
Gold nanoparticles (GNPs) have been reported to exhibit a variety of biological effects including anti-
inammatory and anti-oxidant activities. The extent of an in vitro glycation reaction mixture of collagen
and glycolaldehyde was assayed to investigate the inhibition of glycolaldehye-derived advanced glycation end
products (glycol-AGEs) formation with GNPs in collagen, which is a major protein component of the human
dermis. GNP-treated collagen showed signicantly less glycation (56.34.2%) than an untreated glycation
control. Moreover, GNP-treated glycation in a collagen lattice model signicantly decreased the AGEs distri-
bution in the model system. Taken together, these results suggest that GNPs have the potential for use in the
prevention of glycation-induced skin aging.
Key words gold nanoparticle; glycation; collagen; dermis; aging
Skin aging is the result of genetic intrinsic chronologi-
cal aging and extrinsic aging due to external factors. One of
the causes of aging is the appearance of advanced glycation
end products (AGEs).1) AGEs are formed by chemical reac-
tion of carbohydrates with protein in a process known as the
Maillard or glycation reaction.2) This reaction begins with
adduction of a reducing sugar to an amino group in protein,
typically the ε-amino group of a lysine residue, to form a
Schiff base, which then rearranges to an Amadori compound.
The Amadori product is a precursor to AGEs, which are a
more permanent, irreversible modication of proteins. AGEs
modications of proteins may lead to alterations in normal
function by inducing cross-linking of extracellular matrices.3)
In the current study, glycolaldehye-derived AGEs (GA-AGEs)
was used as a source of AGEs. It appears that short chain sug-
ars such as GA could play an important role as intermediates
in the formation of AGE structures in the glycation reaction.4)
Based on immunoreactivity, GA-pyridine having a GA-AGE
structure is reported to be the most signicant AGE for car-
tilage degredation though AGE-its specic receptor (R AGE)-
oxidative stress axis.5)
A number of compounds have been introduced as AGE
inhibitors based on their inhibition of AGE formation during
incubation of proteins with glucose in vitro. These inhibitors
vary widely in structure, the common theme being their nu-
cleophilicity or reactivity with reactive carbonyl intermediates
in AGE formation. Aminoguanidine (AG) has been suggested
as a representative agent for the inhibition of glycation,6) al-
though clinical trials for this compound were stopped due to
reported side effects. Gold nanoparticles (GNPs) have been
reported to exhibit a variety of biological activities, includ-
ing anti-imammatory and anti-oxidant activities.710) GNPs,
which represent an emerging nanomedicine, are renowned
for their promising therapeutic possibilities, which include
biocompatibility, high surface reactivity, anti-oxidation and
plasmon resonance.11)
In the present study, we investigated the inhibitory effect on
AGE formation with GNPs in glycation between collagen, a
major protein component of the human dermis and GA.
Preparation of GNPs GNPs were prepared using the
method described by Storhoff et al.12) All glassware was
cleaned in aqua regia (3 parts HCl and 1 part HNO3), rinsed
with nanopure water, and then oven dried prior to use. A total
of 500 mL of 2 mM chlorauric acid (HAuCl4) aqueous solution
was brought to a reux while stirring, after which 50 mL of
38.8 mM trisodium citrate solution was rapidly added. This
resulted in a change in solution color from pale yellow to deep
red. After the color change, the solution was reuxed for an
additional 15 min, allowed to cool to room temperature, and
subsequently ltered through a 0.45 μm nylon lter (Micro
Filtration System Inc., CA, U.S.A.). The absor ption spectra
was measured for characterization of GNPs.13)
Transmission Electron Microscopic Studies Transmis-
sion electron microscopy (TEM) conducted using a JEOL
100CX transmission electron microscope (JEOL, Tokyo,
Japan) was used to determine the size and monodispersity
of the resulting nanoparticle solutions. Images of GNPs in
aqueous dispersions were examined after placing drops of the
dispersion onto 400 mesh gold grids and allowing the liquid to
dry at 28°C.14)
Pre-glycation of Collagen Solution Pre-glycation of
collagen solution was modied using the method described
by Rahbar et al.15) Briey, collagen solution (3 mg/mL, Nitta
Gelatin Inc., Osaka, Japan) and 10 mM glycolaldehyde in
N HCl containing 0.02% sodium azide (NaN3) and 1 mM
diethylene triamine pentaacetic acid (DTPA) to obtain a reac-
tion mixture, and the reaction mixture was incubated at 37°C
for 7 d in the presence of GNPs or 5 mM AG. At the end of
the incubation period, dialysis was conducted for 24 h against
N HCl. The glycation of collagen in solution was moni-
tored as follows. An aliquot of the collagen was solubilized
with 1% pepsin at 37°C. After pepsin digestion, the samples
were centrifuged for 5 min at 10000
g and the uorescence
intensity of the digested collagen in the supernatant layer was
then measured at 370 nm/440 nm.16) Table 1 shows the reaction
mixture of pre-glycation collagen solution. Collagen solution
without glycolaldehyde was used as a negative control. The
percent inhibition of AGE formation was calculated using the
* To whom cor respondence should be addressed. e-mail: kwang
# T hese authors contributed equally to this work.
February 2012 261
following equation:
inhibition percentage of AGE formation (%)
100 100
A: Fluorescence of the reaction mixture without glycolalde-
hyde (negative control). B: Fluorescence of the reaction mix-
ture with glycolaldehyde (positive control). C: Fluorescence of
the reaction mixture with GNPs. D: Fluorescence of the reac-
tion mixture with GNPs and without glycolaldehyde.
Determination of Nε-(Carboxymethyl)lysine by HPLC
A reversed-phase-HPLC method17) with o-phtalaldehyde
(OPA) pre-column-derivatization for determination of Nε-
(carboxymethyl)lysine (CML), a representative AGEs marker
was slighltly modied. Briey, 100 mg of the sample was
hydrolyzed with 10 mL of 7.95
M HCl at 105°C for 24 h. After
hydrolysis of sample, it was cooled at room temperature under
N2 gas, and subsequently centrifuged at 14000×g for 15 min.
Sep-pak C18 cartridge (Waters Associates, MA, U.S.A.) was
pre-wetted with 10 mL of methanol and 20 mL of deionized
water (DW) before 1 mL of the super natant was applied to it,
and then eluted with 10 mL of 3
M HCl. OPA reagent (20 μL)
was added to the 20 μL of sample in vial, and vigorous mix-
ing was applied. After 180 s of reaction, 20 μL of derivatised
hydrolysate was analyzed with analytical column (Waters
Spherissorb® 5 μm ODS2 column, 4.6×250 mm) at 32°C.
Mobile phase were composed of (A) DW and (B) MeOH,
and the gradient was linear from 0 to 100% B in 16 min. The
OPA-derivatives were detected uorimetrically at 340 nm
excitation and 455 nm emission. The peak retentation time of
CML standard (PolyPeptide Lab., CA, U.S.A.) was used to
identify the peak of sample constituent.
Construction of Collagen Lattice and Preparation of
Frozen Section A collagen lattice was constructed using
collagen solution (native collagen for control or a 1 : 1 mixture
of pre-glycated and native collagen) and reconstitution buf-
fer (0.05
N NaOH containing 2.2% sodium biscarbonate and
20 mM Hepes buffer solution) at a ratio of 8 : 1.16,18) Collagen
lattices were polymerized by increasing the temperature to
37°C and then incubating the samples for 24 h. The collagen
lattices were subsequently detached from the mold and sub-
merged into liquid nitrogen to ensure that they were com-
pletely frozen. The lattices were then stored in a deep freezer
(70°C) until ready for sectioning. Frozen collagen lattices
were sectioned using cryotome (Leica CM1900, Leica Inc.,
CA, U.S.A.), and then placed onto glass slides for immuno-
uorescence staining.
Immunouorescence Staining for Distribution of AGEs
on Glycated Collagen Lattices Frozen sections of col-
lagen lattices were sectioned at 15 μm. Nonspecic binding
sites were blocked with a 2% (v/v) dilution of appropriate
normal serum in Tris-buffered saline (pH 7.4) in a humidied
chamber. Each sample was subsequently treated with specic
antibodies against AGEs (TransGenic, Kobe, Japan, 2 μg/mL).
Finally, the samples were washed in phosphate buffered sa-
line (PBS), incubated with a goat anti-mouse Alexa 488 uor
Table 1. Reaction Mixture of Pre-glycation of Collagen Solution
Component (nal
concentration) Control (A) Glycation (B) Sample (C) Blank of sample (D)
Collagen (3 mg /mL) 
Glycolaldehyde (10 mM) 
HCl (0.001
DTPA (1 m M)
Sodium azide (0.02%) 
GNPs  
DTPA: diet hylene t riamine pentaa cetic acid, G NPs: gold nanopart icles.
Fig. 1. Absorption Spectra for Gold Nanoparticles (GNPs) and Their Transmission Electron Microscopic (TEM) Image
(A) GNP surface plasmon absorpt ion ba nd was peaked at 520 nm. (B) The diameter of t he GNPs was determined to be approxi mately 2 0 n m.
262 Vol. 35, No. 2
antibody (Invitrogen, Carlsbad, U.S.A., 1 : 200), mounted and
cover slipped. All slides were then examined and evaluated
using a confocal laser scanning microscope (LSM 5 Exciter,
Carl-zeiss, Hamburg, Germany).
Statistical Analysis All data ±S.E.M. Statistical analysis
was performed by analysis of variance (ANOVA), followed by
Duncans multiple range test for the individual comparisons of
the means.
The absorption spectrum of GNPs exhibited a surface plas-
mon absorption band. The position and shape of the plasmon
absorption of metal nano materials are strongly dependent
on the particle size, dielectric medium and surface adsorbed
species.1921) A typical solution of 1322 nm diameter GNPs
exhibited a characteristic surface plasmon absorption band
centered at 518521 nm.22) Our preparation of GNPs produced
a surface plasmon absorption band centered at 520 nm (Fig.
1A). Figure 1B shows the GNPs based on TEM observation
having a 20 nm of diameter.
It has been reported that AG has two key reaction centers:
the nucleophilic hydrazine group –NHNH2 and the dicarbon-
yl-directing guanido group –NH–C(=NH)NH2 and these two
groups together are involved in preventing the formation of
AGEs from α,β-dicarbonyl precursors.23) On the other hand,
the activity of GNPs against glycation may come from com-
petitively binding to the free amino groups of Lys and Arg
which are potent sites for glycation.24) Figure 2A shows the
inhibitory effects of AG and GNPs on glycated collagen in
the presence of GNPs. AG treated glycation of collagen solu-
tion and GNP-treated glycation of collagen showed signicant
glycation inhibition (64.0±5.7, 56.3±4.2%, respectively) when
compared with non-treated glycation control. In addition, the
levels of CML on glycated collagen were measured (Fig. 2B).
CML has been repor ted as a representative AGEs marker in
vivo and foods.25) The treatments of AG and GNPs signi-
cantly inhibited the formation of CML (63.1±8.2, 38.2±7.7%,
respectively) compared with non-treated glycation control.
Figure 3 shows immunouorescence staining for the distri-
bution of AGEs on glycated collagen lattices in each group.
The AGEs immunoreactivity in the collagen lattices were
found to be elevated in the glycation group (Fig. 3B) when
compared with the control group (Fig. 3A). After the addition
of 5 mM AG (Fig. 3C) or GNPs (Fig. 3D) to the glycation col-
lagen solution, the intensity of the AGE staining was signi-
cantly lower than that of the non-treated glycation group.
AGEs can mediate their effects via specic receptors, in-
cluding generation of reactive oxygen species (ROS). ROS
radicals can affect various cellular pathways and gene ex-
pression.26) Through this pathway, AGEs alter the structural
properties of tissue proteins and reduce their susceptibility to
catabolism.27 ) In the preliminary experiment, 2,7-dichlorou-
orescin diacetate (DCFDA)-loaded keratinocytes (HaCaT) in-
cubated with 200 μg/mL of GA-AGEs increased the increased
intracellular reactive oxygen species 1.7-fold compared with
bovine serum albumin control. Antioxidant reagents are
known to lead to signicant decreases in oxidation stress due
to ROS. Yakimovich et al. demonstrated that GNPs have anti-
oxidant activity.28)
The dermal matrix of skin consists of collagen, elastin and
broblast. AGEs alter the mechanical proper ties of the skin
by modifying macromolecules and the biological properties of
the resident cells.1) Alikhani et al. reported that AGEs stimu-
late broblast apoptosis in vivo,29) and AGEs accumulation
is known to cause chronological skin aging.30) Collagens are
important proteins for the skin because they are essential for
the structure and function of the extracellular matrix in the
dermis. AGEs accumulation of the dermis collagen contributes
to protein aggregation, and increases the expressions of metal-
loproteinases, which degrade the collagen, and subsequently
leads to skin aging.
The results presented here demonstrate that GNPs exhib-
ited an AGE inhibitory effect. In future studies, we propose
development of a reconstituted skin model that consists of a
broblast cell, keratinocytes and collagen lattice. We will then
apply GNPs to this reconstituted skin model to investigate the
mechanism of the skin anti-aging action of GNPs in detail.
Acknowledgement This research was supported by
Technology Development Program for Agriculture and
Forestry, Ministry for Food, Agriculture, Forestry and
Fisheries, Repulic of Korea (IPET, Grant 109140032SB010).
The authors thank the Korea University-CJ Food Safety
Fig. 2. In hibitory Effects of GNPs on Glycation and Nε-(Carboxymethyl)lysine (CML) For mation
(A) Anti-glycation effect of GNPs was determi ned by the collagen–glycola ldehyde a ssay. (B) CML c ontents were deter mined by HPLC. Values represent mea n±S.E.M.
(n=3 in e ach group). *p<0.05, **p<0.01, compa red with the values of control group. D ifferent letters above t he ba r i n t he g roups indicate statistically signicant differ-
ences by Du ncans multiple range t est ( p<0.05). Control g roup: colla gen only; Glycation group: collagen with glycolaldehyde; AG group: col lagen and glycolald ehyde wit h
5 mM aminoguanidi ne (AG); GNP group: collagen and glycolaldehyde w ith GN Ps.
February 2012 263
Center (Seoul, South Korea) for providing the equipment and
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A (contr ol group): collagen only; B (glycation group): collagen with glycolald ehyde; C (AG group): colla gen and glycolaldehyde with 5 mM AG; D (GNP group): collagen
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... Singha et al. (2009) studied the anti-glycating activity of AuNPs on eye protein α-crystallin, suggesting its possible utility to inhibit cataract formation. Kim et al. (2012) also investigated the inhibitory effect of the 20 nm AuNPs of the glycation of collagen, a major protein component of the human dermis. Liu et al. (2014) studied the inhibitory effect of citrate coated spherical AuNPs (ranging from 2 nm to 20 nm) on the glycation of bovine serum albumin (BSA's) by D-ribose. ...
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... The essential core structures of NP-functionalized NMs ensure drug encapsulation or conjugation, as well as protection and sustained blood circulation Leszek et al. (2017). NMs can also target cells or even an intracellular compartment such as Aβ in cells, allowing the drug to be delivered at a predetermined dosage straight to the diseased spot Kim et al. (2012). NMs can reduce the dose and frequency of treatment, resulting in better patient compliance Altinoglu and Adali (2020). ...
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Over the years, Alzheimer’s disease (AD) treatments have been a major focus, culminating in the identification of promising therapeutic targets. A herbal therapy approach has been required by the demand of AD stage-dependent optimal settings. Present study describes the evaluation of anti-acetylcholinesterase (AChE) activity of hydroxyapatite nanoparticles derived from an Acorus calamus rhizome extract (AC-HAp NPs). The structure and morphology of as-prepared (AC-HAp NPs) was confirmed using powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM). The crystalline nature of as-prepared AC-HAp NPs was evident from XRD pattern. The SEM analysis suggested the spherical nature of the synthesized material with an average diameter between 30 and 50 nm. Further, the TEM and HR-TEM images revealed the shape and size of as-prepared (AC-HAp NPs). The interplanar distance between two lattice fringes was found to be 0.342 nm, which further supported the crystalline nature of the material synthesized. The anti-acetylcholinesterase activity of AC-HAp NPs was greater as compared to that of pure HAp NPs. The mechanistic evaluation of such an activity carried out using in silico studies suggested that the anti-acetylcholinesterase activity of phytoconstituents derived from Acorus calamus rhizome extract was mediated by BNDF, APOE4, PKC-γ, BACE1 and γ-secretase proteins. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H2O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. With the further objective of analyzing their bioactivity, the CDFT studies are complemented with the estimation of some useful computed pharmacokinetics indices, their predicted biological targets, and the ADMET parameters related to the bioavailability of the five ligands are also reported.
... Nanomedicines have the advantages of reduced dimensions and increased biocompatibility that facilitate easy transport of therapeutic substances into the brain (Spuch et al., 2012;Fakhoury et al., 2015;Leszek et al., 2017). Small-size (approximately 100-10,000 times smaller than a human cell) nanomedicines can easily interact with the proteins and molecules on the cell surface as well as inside the cell (Kim et al., 2012). NP-functionalized nanomedicines have central core structures that ensure the encapsulation or conjugation of drugs and provide the protection and prolonged circulation in the blood (Knop et al., 2010;. ...
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Advanced glycation end products (AGEs) are among the series factors that cause the pathology of neurodegenerative diseases. Carbon dots (CDs) with low toxicity, tunable surface chemistry and biocompatibility have been used for biological inhibition and as anticancer agents. In this study, CDs derived from highland barley bran (HBB-CDs) were used to inhibit the formation of AGEs in vitro in vitro. and The possible inhibitory mechanism was attributed to the decreased number of glycosylation sites in glycosylated β-casein from four and six to three and four in the presence of the HBB-CDs, which was revealed by HPLC–Orbitrap tandem mass spectrometry at the molecular level. explored at the molecular level. After 12 h and 24 h in the existence of HBB-CDs, the number of glycosylation sites in glycosylated β-casein decreased from four and six to three and four by using HPLC–Orbitrap tandem mass spectrometry. Furthermore, the glycosylation degree of every each glycosylation site was commanded, and the double saccharification capacity of K167 and K214 was changed. Strong inhibition of AGEs formation in the presence of elevated HBB-CDs suggested that CDs are potential anti-glycation agents and food additives for against glycation-associated diseases and food processing.
Alzheimer’s disease is a progressive neurodegenerative diseases that causes brain-associated problems with memory, thinking, and behavior. Alzheimer’s disease is the most common form of dementia. According to the World Health Organization, 10 million new instances of dementia are recorded each year worldwide, with 60%–70% of these cases possibly leading to Alzheimer's disease. Currently, most treatment approaches are based on maintaining mental functions, managing behavioral symptoms, and slowing or delaying disease progression. This chapter focuses on diagnosis, neuropathogenesis, and all possible nano drug delivery approaches for its treatment.
Aging is an inevitable process caused by the accumulation of degenerative destructions, which ultimately leads to organism death. As the aging process occurs at the molecular, cellular, and tissue levels, understanding the whole details of age-related disorders is the prerequisite for the development of anti-aging therapy. More than 300 compounds of different sources have been reported with an anti-aging activity that controls age-related diseases through regulating single or multiple signalling pathways. Recent innovations in nanotechniques could lead to the development of nanomaterials having effects on age-associated malfunctions or acting as nanocarrier systems and distributers of anti-aging drugs. In this review, we summarised the molecular mechanisms of longevity and the prospect of developing anti-aging nanomaterials targeting aging pathways.
The role of cosmetic products is rapidly evolving in our society, with their use increasingly seen as an essential contribution to personal wellness. This suggests the necessity of a detailed elucidation of the use of nanoparticles (NPs) in cosmetics. The aim of the present work is to offer a critical and comprehensive review discussing the impact of exploiting nanomaterials in advanced cosmetic formulations, emphasizing the beneficial effects of their extensive use in next-generation products despite a persisting prejudice around the application of nanotechnology in cosmetics. The discussion here includes an interpretation of the data underlying generic information reported on the product labels of formulations already available in the marketplace, information that often lacks details identifying specific components of the product, especially when nanomaterials are employed. The emphasis of this review is mainly focused on skincare because it is believed to be the cosmetics market sector in which the impact of nanotechnology is being seen most significantly. To date, nanotechnology has been demonstrated to improve the performance of cosmetics in a number of different ways: 1) increasing both the entrapment efficiency and dermal penetration of the active ingredient, 2) controlling drug release, 3) enhancing physical stability, 4) improving moisturizing power, and 5) providing better UV protection. Specific attention is paid to the effect of nanoparticles contained in semisolid formulations on skin penetration issues. In light of the emerging concerns about nanoparticle toxicity, an entire section has been devoted to listing detailed examples of nanocosmetic products for which safety has been investigated.
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The Au-containing nanocomposites were synthesized by UV irradiation followed by the thermal treatment of chitosan oligomer solutions doped by HAuCl4. The size of the formed gold nanoparticles depends on the concentration of the dopant, which is proved by UV—Vis absorption spectroscopy and small-angle X-ray scattering (SAXS). The antioxidant activity of the gold nanoparticles with respect to hydroxy radicals significantly depends on the specific surface of the particles, which was found using the secondary radical spin-trapping technique. The change in the ·OH radical concentration was monitored by the intensity of the ESR signal of the adduct of the spin trap (α-phenyl-N-tert-butylnitrone) with the Me·radicals formed in the reaction of ·OH with DMSO.
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Oxidative stress is imperative for its morbidity towards diabetic complications, where abnormal metabolic milieu as a result of hyperglycemia, leads to the onset of several complications. A biological antioxidant capable of inhibiting oxidative stress mediated diabetic progressions; during hyperglycemia is still the need of the era. The current study was performed to study the effect of biologically synthesized gold nanoparticles (AuNPs) to control the hyperglycemic conditions in streptozotocin induced diabetic mice. The profound control of AuNPs over the anti oxidant enzymes such as GSH, SOD, Catalase and GPx in diabetic mice to normal, by inhibition of lipid peroxidation and ROS generation during hyperglycemia evidence their anti-oxidant effect during hyperglycemia. The AuNPs exhibited an insistent control over the blood glucose level, lipids and serum biochemical profiles in diabetic mice near to the control mice provokes their effective role in controlling and increasing the organ functions for better utilization of blood glucose. Histopathological and hematological studies revealed the non-toxic and protective effect of the gold nanoparticles over the vital organs when administered at dosage of 2.5 mg/kilogram.body.weight/day. ICP-MS analysis revealed the biodistribution of gold nanoparticles in the vital organs showing accumulation of AuNPs in the spleen comparatively greater than other organs. The results obtained disclose the effectual role of AuNPs as an anti-oxidative agent, by inhibiting the formation of ROS, scavenging free radicals; thus increasing the anti-oxidant defense enzymes and creating a sustained control over hyperglycemic conditions which consequently evoke the potential of AuNPs as an economic therapeutic remedy in diabetic treatments and its complications.
1. Introduction.- 2. Theoretical Considerations.- 3. Experimental Methods.- 4. Experimental Results and Discussion.- A.1 Tables: Optical Spectroscopy Experiments with Metal Clusters.- A.2 Survey of Optical Spectra of Elemental Metal Clusters and Chain-Aggregates.- A.3 Mie Computer Program.- References.
The size and temperature dependence of the plasmon absorption is studied for 9, 15, 22, 48, and 99 nm gold nanoparticles in aqueous solution. The plasmon bandwidth is found to follow the predicted behavior as it increases with decreasing size in the intrinsic size region (mean diameter smaller than 25 nm), and also increases with increasing size in the extrinsic size region (mean diameter larger than 25 nm). Because of this pronounced size effect a homogeneous size distribution and therefore a homogeneous broadening of the plasmon band is concluded for all the prepared gold nanoparticle samples. By applying a simple two-level model the dephasing time of the coherent plasmon oscillation is calculated and found to be less than 5 fs. Furthermore, the temperature dependence of the plasmon absorption is examined. A small temperature effect is observed. This is consistent with the fact that the dominant electronic dephasing mechanism involves electron−electron interactions rather than electron−phonon coupling.
Aminoguanidine (AG) is a prototype therapeutic agent for the prevention of formation of advanced glycation endproducts. It reacts rapidly with alpha,beta-dicarbonyl compounds such as methylglyoxal, glyoxal, and 3-deoxyglucosone to prevent the formation of advanced glycation endproducts (AGEs). The adducts formed are substituted 3-amino-1,2,4-triazine derivatives. Inhibition of disease mechanisms, particularly vascular complications in experimental diabetes, by AG has provided evidence that accumulation of AGEs is a risk factor for disease progression. AG has other pharmacological activities, inhibition of nitric oxide synthase and semicarbazide-sensitive amine oxidase (SSAO), at pharmacological concentrations achieved in vivo for which controls are required in anti-glycation studies. AG is a highly reactive nucleophilic reagent that reacts with many biological molecules (pyridoxal phosphate, pyruvate, glucose, malondialdehyde, and others). Use of high concentrations of AG in vitro brings these reactions and related effects into play. It is unadvisable to use concentrations of AG in excess of 500 microM if selective prevention of AGE formation is desired. The peak plasma concentration of AG in clinical therapy was ca. 50 microM. Clinical trial of AG to prevent progression of diabetic nephropathy was terminated early due to safety concerns and apparent lack of efficacy. Pharmacological scavenging of alpha-oxoaldehydes or stimulation of host alpha-oxoaldehyde detoxification remains a worthy therapeutic strategy to prevent diabetic complications and other AGE-related disorders.
The design and initial characterization of two-dimensional arrays of colloidal Au particles are reported. These surfaces are prepared by self-assembly of 12 nn diameter colloidal Au particles onto immobilized polymers having pendant functional groups with high affinity for Au (i.e., CN, SH, and NH2). The polymers are formed by condensation of functionalized alkoxysilanes onto cleaned quartz, glass, and SiO2 surfaces. The assembly protocol is carried out completely in solution: cleaned substrates are immersed in methanolic solutions of organosilane, rinsed, and subsequently immersed in aqueous colloidal Au solutions. Two-dimensional arrays spontaneously form on the polymer surface, The resulting substrates have been characterized by UV-vis spectroscopy, transmission electron microscopy (TEM), and surface-enhanced Raman scattering (SERS). TEM data show that the particles are spatially separated but close enough to interact electromagnetically (small spacing compared to lambda). The UV-vis data show that collective particle surface plasmon modes are present in the 650-750 nm region, suggesting that these assemblies are SERS-active. This is indeed the case, with enhancement factors of roughly 10(4). Au colloid monolayers possess a set of features that make them very attractive for both basic and applied uses, including uniform roughness, high stability, and biocompatibility.
Selective colorimetric polynucleotide detection based on Au nanoparticle probes which align in a "tail-to-tail" fashion onto a target polynucleotide is described. In this new nanoparticle-based detection system, Au particles (∼13 nm diameter), which are capped with 3′-and 5′-(alkanethiol)oligonucleotides, are used to complex a 24-base polynucleotide target. Hybridization of the target with the probes results in the formation of an extended polymeric Au nanoparticle/polynucleotide aggregate, which triggers a red to purple color change in solution. The color change is due to a red shift in the surface plasmon resonance of the Au nanoparticles. The aggregates exhibit characteristic, exceptionally sharp "melting transitions" (monitored at 260 or 700 nm), which allows one to distinguish target sequences that contain one base end mismatches, deletions, or an insertion from the fully complementary target. When test solutions are spotted onto a C18 reverse-phase thin-layer chromatography plate, color differentiation is enhanced and a permanent record of the test is obtained, thereby providing a better method for distinguishing the aforementioned target sequences. Significantly, one-pot colorimetric detection of the target in the presence of four strands with single base imperfections can be accomplished with this new probe system.
Advanced glycation end products (AGEs) may be associated with osteoarthritis (OA), because the accumulation of AGEs in articular cartilage are among the most striking age-related changes. AGEs modify the tissue protein structure and function and stimulate the cellular responses mediated by a specific receptor for AGEs (RAGE). This study investigated the localization of AGEs in degenerated cartilage using newly identified epitope-specific antibodies to determine the linkage between the distribution of AGEs and the development and progression of OA. Osteochondral specimens of the tibial plateau from OA patients were immunostained by specific antibodies against N(ε)-(carboxymethyl)lysine (CML), N(ε)-(carboxyethyl)lysine (CEL), pentosidine, GA-pyridine, and RAGE. The immunohistochemical distribution of these epitopes was evaluated during cartilage degeneration. The immunoreactivity (IR) of AGEs and RAGE was stronger in cells rather than in the extracellular matrix. Higher IR of cellular CML and CEL was observed in both mild and severe OA cartilage in comparison to macroscopically intact cartilage. There was a strong association between GA-pyridine and RAGE in the pattern of increasing IR with the OA grade. These IR patterns of AGEs varying with cartilage degeneration indicate that AGE modified proteins are associated with cartilage degeneration. The coincidental up-regulation of GA-pyridine and RAGE suggests that GA-pyridine is the most significant AGE for cartilage degeneration via the RAGE pathway.