The effects of gold nanoparticles in wound healing with antioxidant epigallocatechin gallate and α-lipoic acid.

UNLABELLED Topical applications of antioxidant agents in cutaneous wounds have attracted much attention. Gold nanoparticles (AuNPs), epigallocatechin gallate (EGCG), and α-lipoic acid (ALA) were shown to have antioxidative effects and could be helpful in wound healing. Their effects in Hs68 and HaCaT cell proliferation and in mouse cutaneous wound healing were studied. Both the mixture of EGCG + ALA (EA) and AuNPs + EGCG + ALA (AuEA) significantly increased Hs68 and HaCaT proliferation and migration. Topical AuEA application accelerated wound healing on mouse skin. Immunoblotting of wound tissue showed significant increase of vascular endothelial cell growth factor and angiopoietin-1 protein expression, but no change of angiopoietin-2 or CD31 after 7 days. After AuEA treatment, CD68 protein expression decreased and Cu/Zn superoxide dismutase increased significantly in the wound area. In conclusion, AuEA significantly accelerated mouse cutaneous wound healing through anti-inflammatory and antioxidation effects. This study may support future studies using other antioxidant agents in the treatment of cutaneous wounds. FROM THE CLINICAL EDITOR In this study, topically applied gold nanoparticles with epigallocatechin gallate and alpha-lipoic acid were studied regarding their effects in wound healing in cell cultures. Significant acceleration was demonstrated in wound healing in a murine model.

[1]  Naoki Toshima,et al.  Platinum nanoparticle is a useful scavenger of superoxide anion and hydrogen peroxide , 2007, Free radical research.

[2]  M. Mattson,et al.  Involvement of Notch Signaling in Wound Healing , 2007, PloS one.

[3]  G. Marti,et al.  Current Insights into the role of HIF-1 in cutaneous wound healing. , 2011, Current molecular medicine.

[4]  M. Brownlee,et al.  Effect of R-(+)-α-lipoic acid on experimental diabetic retinopathy , 2006, Diabetologia.

[5]  Alex F Chen,et al.  Gene Therapy of Endothelial Nitric Oxide Synthase and Manganese Superoxide Dismutase Restores Delayed Wound Healing in Type 1 Diabetic Mice , 2004, Circulation.

[6]  D. Astruc,et al.  Gold Nanoparticles: Assembly, Supramolecular Chemistry, Quantum‐Size‐Related Properties, and Applications Toward Biology, Catalysis, and Nanotechnology. , 2004 .

[7]  J. Varani,et al.  Pretreatment of diabetic rats with lipoic acid improves healing of subsequently-induced abrasion wounds , 2005, Archives of Dermatological Research.

[8]  V. Wagh,et al.  Chemoprotective mechanism of the natural compounds, epigallocatechin-3-O-gallate, quercetin and curcumin against cancer and cardiovascular diseases. , 2009, Current medicinal chemistry.

[9]  L. Packer,et al.  Neuroprotection by the Metabolic Antioxidant α-Lipoic Acid , 1997 .

[10]  Dongwook Han,et al.  Enhanced wound healing by an epigallocatechin gallate‐incorporated collagen sponge in diabetic mice , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[11]  Song-Hee Kim,et al.  Gold Nanoparticles Inhibited the Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-Induced Osteoclast Formation by Acting as an Antioxidant , 2010, Bioscience, biotechnology, and biochemistry.

[12]  E. Feskens,et al.  Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study , 1993, The Lancet.

[13]  V. Adhami,et al.  Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis , 2008, Oncogene.

[14]  S. Werner,et al.  Wound repair and regeneration , 1994, Nature.

[15]  Stata Norton,et al.  A brief history of potable gold. , 2008, Molecular interventions.

[16]  H. García,et al.  Nano-jewels in biology. Gold and platinum on diamond nanoparticles as antioxidant systems against cellular oxidative stress. , 2010, ACS nano.

[17]  D. Noonan,et al.  Biological assays and genomic analysis reveal lipoic acid modulation of endothelial cell behavior and gene expression. , 2006, Carcinogenesis.

[18]  C. Milne Wound healing in older adults: unique factors should guide treatment. , 2008, Advance for nurse practitioners.

[19]  S. Sheikpranbabu,et al.  RETRACTED ARTICLE: Gold nanoparticles inhibit vascular endothelial growth factor-induced angiogenesis and vascular permeability via Src dependent pathway in retinal endothelial cells , 2011, Angiogenesis.

[20]  O. Salata,et al.  Applications of nanoparticles in biology and medicine , 2004, Journal of nanobiotechnology.

[21]  M. Namaka,et al.  Examining the evidence: complementary adjunctive therapies for multiple sclerosis , 2008, Neurological research.

[22]  A. Singer,et al.  Cutaneous wound healing. , 1999, The New England journal of medicine.

[23]  J. H. Kim,et al.  The inhibition of retinal neovascularization by gold nanoparticles via suppression of VEGFR-2 activation. , 2011, Biomaterials.

[24]  Q. Pankhurst,et al.  Applications of magnetic nanoparticles in biomedicine , 2003 .

[25]  J. Neuzil,et al.  α-Lipoic Acid Modulates Extracellular Matrix and Angiogenesis Gene Expression in Non-Healing Wounds Treated with Hyperbaric Oxygen Therapy , 2008 .

[26]  Z. Nie,et al.  Enhanced radical scavenging activity by antioxidant-functionalized gold nanoparticles: a novel inspiration for development of new artificial antioxidants. , 2007, Free radical biology & medicine.

[27]  Y. Kim,et al.  Recombinant Human Epidermal Growth Factor (EGF) to Enhance Healing for Diabetic Foot Ulcers , 2006, Annals of plastic surgery.

[28]  F. Sánchez-Jiménez,et al.  Targeting of histamine producing cells by EGCG: a green dart against inflammation? , 2010, Journal of Physiology and Biochemistry.

[29]  Jianxin Wang,et al.  Co-administration of protein drugs with gold nanoparticles to enable percutaneous delivery. , 2010, Biomaterials.

[30]  Manuela Semmler-Behnke,et al.  Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration , 2011, Nanotoxicology.

[31]  L. Packer,et al.  Neuroprotection by the metabolic antioxidant alpha-lipoic acid. , 1997, Free radical biology & medicine.

[32]  J. Daly Timing of Administration of Bevacizumab Chemotherapy Affects Wound Healing After Chest Wall Port Placement , 2011 .

[33]  V. Pokharkar,et al.  Chitosan-reduced gold nanoparticles: a novel carrier for the preparation of spray-dried liposomes for topical delivery , 2011, Journal of liposome research.

[34]  D. Bickers,et al.  Green tea protects against psoralen plus ultraviolet A-induced photochemical damage to skin. , 1999, The Journal of investigative dermatology.

[35]  Ö. Yılmaz,et al.  Effects of alpha lipoic acid, ascorbic acid‐6‐palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats , 2002, Journal of cellular biochemistry.

[36]  O. Branford,et al.  The effect of epigallocatechin‐3‐gallate, a constituent of green tea, on transforming growth factor‐β1–stimulated wound contraction , 2010, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[37]  Joseph L Evans,et al.  Beneficial effects of natural antioxidants EGCG and α-lipoic acid on life span and age-dependent behavioral declines in Caenorhabditis elegans , 2006, Pharmacology Biochemistry and Behavior.

[38]  H. Kataoka,et al.  Chromatographic analysis of lipoic acid and related compounds. , 1998, Journal of chromatography. B, Biomedical sciences and applications.

[39]  D. Maes,et al.  Anti-angiogenic effects of epigallocatechin-3-gallate in human skin. , 2010, International journal of clinical and experimental pathology.