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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.
MATERIALS AND METHODS
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
0.001
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
0.001
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
Note
* To whom cor respondence should be addressed. e-mail: kwang won@korea.ac.kr
# T hese authors contributed equally to this work.
February 2012 261
following equation:
inhibition percentage of AGE formation (%)
()
100 100
()
CD
BA






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
N)
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.
RESULTS AND DISCUSSION
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
facilities.
REFERENCES
1) Pageon H. Reaction of glycation and human skin: the effects on
the skin and its components, reconstr ucted skin as a model. Pathol.
Biol. (Paris), 58, 226 231 (2010).
2) Tan AL, Forbes J M, Cooper ME. AGE, R AGE, and ROS in diabetic
nephropathy. Semin. Nephrol., 27, 130143 (2007).
3) Thorpe SR, Baynes JW. Role of the Maillard reaction in diabetes
mellitus and diseases of aging. Drugs Aging, 9, 6977 (1996).
4) Takeuchi M, Makita Z, Bucala R, Suzu ki T, Koike T, Kameda Y.
Immunological evidence that non-carboxymethyllysine advanced
glycation end-products are produced from short chain sugars and
dicarbonyl compounds in vivo. Mol. Med., 6, 114125 (2000).
5) Hirose J, Yamabe S, Takada K, Okamoto N, Nagai R, Mizuta H.
Immunohistochemical distribution of advanced glycation end prod-
ucts (AGEs) in human osteoart hritic cartilage. Acta Histochem.,
113, 613618 (2011).
6) Brownlee M, V lassara H, Kooney A, U lrich P, Cerami A.
Aminoguanidine prevents diabetes-induced arterial wall protein
cross-linking. Science, 232, 16291632 (1986).
7) Jeon KI, Byun MS, Jue DM. Gold compound auranon in hibits
IkappaB kinase (IKK) by modif ying Cys-179 of IKKbeta subunit.
Exp. Mol. Med., 35, 6166 (2003).
8) Kim NH, Lee MY, Park SJ, Choi JS, Oh MK, Kim IS. Auranon
blocks interleuki n-6 signalling by inhibiting phosphor ylation of
JAK1 and STAT3. Immunology, 122, 607614 (2007).
9) Norton S. A brief history of potable gold. Mol. Interv., 8, 120123
(2008).
10) Barathmanikanth S, K alishwaralal K , Sr iram M, Pandian SR, Youn
HS, Eom S, Gurunathan S. Anti- oxidant effect of gold nanopar-
ticles restrains hyperglycemic conditions in diabetic mice. J.
Nanobiotechnol., 8, 1630 (2010).
11) Guo R, Song Y, Wang G, Mur ray RW. Does core size matter in the
kinetics of liga nd exchanges of monolayer-protected Au clusters? J.
Am. Chem. Soc., 127, 27522757 (2005).
12) Storhoff JJ, Elghania n R, Mucic RC, Mirkin CA, Letsinger RL.
One-pot colorimetric differentiation of polynucleotides with single
base imperfections using gold nanopar ticle probes. J. Am. Chem.
Soc., 120, 19591964 (1998).
13) Grabar KC, Freeman RG, Hommer MB, Natan MJ. Preparation
and cha racter ization of Au colloid monolayers. Anal. Chem., 67,
735743 (1995).
14) Ghoshmoulick R, Bhat tachar ya J, Mitra CK, Basak S, Da sgupta
AK. Protein seeding of gold nanopar ticles and mechanism of glyca-
tion sensing. Nanomedicine, 3, 208214 (2007).
15) Rahbar S, Yerneni KK, Scott S, Gonzales N, Lalezari I. Novel in-
hibitors of advanced glycation endproducts (par t II). Mol. Cell Biol.
Res. Commun., 3, 360366 (2000).
16) Pageon H, Bakala H, Mon nier VM, Asselineau D. Collagen glyca-
tion triggers the format ion of aged skin in vitro. Eur. J. Dermatol.,
17, 1220 (2007).
17) Delgado-Andrade C, Seiquer I, Navarro MP, Morales FJ. Maillard
reaction indicators in diets usually consumed by adolescent popula-
tion. Mol. Nutr. Food Res., 51, 341351 (2007).
18) Pageon H, Técher MP, Asselineau D. Reconst ructed skin modied
by glycation of the dermal equivalent as a model for skin aging
and its potential use to evaluate ant i-glycation molecules. Exp.
Gerontol., 43, 584588 (2008).
19) Thomas KG, Kamat PV. Making gold na nopart icles glow: Enhanced
emission from a sur face-bound uoroprobe. J. Am. Chem. Soc., 122,
Fig. 3. Distribution of AGEs on Glycated Collagen Lat tice
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
and glycolaldehyde with GNPs . Gray tone shows the dist ribution of AGEs. Im munohistochemical s tain; original magni cation, ×200.
264 Vol. 35, No. 2
26552656 (2000).
20) Kreibig U, Vollmer M. Optical Properties of Metal Clusters. Vol.
25, Springer, Berlin, 1995.
21) Peli zzetti E, Pelizzetti E. Fine Particles Science and Technolog y:
From Micro to Nanopart icles. Kluwer Academic Publishers,
Dordrecht (1996).
22) Link S, El-Sayed MA. Size and temperature dependence of the
plasmon absorption of colloidal gold nanopar ticles. J. Phys. Chem.
B, 103, 42124217 (1999).
23) Thornalley PJ. Use of aminoguanidine (Pimagedine) to prevent
the formation of advanced glycation endproducts. Arch. Biochem.
Biophys., 419, 3140 (2003).
24) Singha S, Bhatt acharya J, Datta H, Dasgupta AK. Anti-glycation
activit y of gold nanoparticles. Nanomed-Nanotechnol., 5, 2129
(2009).
25) Ames JM. Determination of Nε-(carboxymethyl)lysine in foods and
related systems. Ann. N.Y. Acad. Sci., 1126, 2024 (2008).
26) Svobodova A, Walterova D, Vostalova J. Ultraviolet light induced
alterat ion to the sk in. Biomed. Pap. Med. Fac. Univ. Palacky
Olomouc Czech Repub., 150, 2538 (2006).
27) Monnier VM, Kohn RR, Cerami A. Accelerated age-related brown-
ing of human collagen in diabetes mellitus. Proc. Natl. Acad. Sci.
U.S.A., 81, 583587 (1984).
28) Yakimovich NO, Ezhevskii AA, Guseinov DV, Smirnova LA,
Gracheva TA, Klychkov KS. Antioxidant properties of gold
nanoparticles studied by ESR spectroscopy. Russ. Chem. Bull., Int.
Ed., 57, 520523 (2008).
29) Alikhani Z, Alik hani M, Boyd CM, Nagao K , Trackma n PC,
Graves DT. Advanced glycation end products enhance expression
of pro-apoptotic genes and stimulate broblast apoptosis t hrough
cytoplasmic and mitochondrial pathways. J. Biol. Chem ., 280,
1208712095 (2005).
30) Verzijl N, DeGroot J, Thorpe SR, Bank RA, Shaw JN, Lyons TJ,
Bijlsma JW, Lafeber FP, Baynes JW, TeKoppele JM. Effect of col-
lagen turnover on t he accumulation of advanced glycation end prod-
ucts. J. Biol. Chem ., 275, 3902739031 (2000).
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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.
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