Alpha-Lipoic Acid Prevents Side Effects of Therapeutic Nanosilver without Compromising Cytotoxicity in Experimental Pancreatic Cancer

被引：6

作者：

An, Xuefeng ^{[1
]}

Liu, Li ^{[1
]}

Schaefer, Michael ^{[1
]}

Yan, Bin ^{[1
]}

Scholz, Christian ^{[2
]}

Hillmer, Stefan ^{[3
]}

Wang, Kangtao ^{[1
]}

Luo, Yiqiao ^{[1
]}

Ji, Huihui ^{[1
]}

Gladkich, Jury ^{[1
]}

Herr, Ingrid ^{[1
]}

机构：

[1] Heidelberg Univ, Dept Gen Visceral & Transplant Surg, Sect Surg Res, Mol OncoSurg, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, Inst Earth Sci, D-69120 Heidelberg, Germany

[3] Heidelberg Univ, Electron Microscopy Core Facil, D-69120 Heidelberg, Germany

来源：

CANCERS | 2021年 / 13卷 / 19期

关键词：

pancreatic cancer; silver nanoparticle; alpha-lipoic acid; chelation; BCAT1; oxidative stress; cytotoxicity; SILVER NANOPARTICLES; ARGYRIA; MICROBIOME; INHIBITION; RESISTANCE; INGESTION; EFFICACY; SAFETY; TISSUE; CELLS;

D O I：

10.3390/cancers13194770

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary: Pancreatic ductal adenocarcinoma is among the most aggressive malignancies and improved treatment options are urgently needed. Silver nanoparticles are suggested as potent antitumor agents, but the side effects of silver overdoses may limit the application. The natural anti-oxidant alpha-lipoic acid might prevent these side effects. We synthesized nanosilver and used it to treat several pancreatic cancer cells and normal cells in the presence or absence of alpha-lipoic acid. Silver selectively eliminated pancreatic cancer cells and alpha-lipoic acid supported the cytotoxicity, whereas benign cells largely resisted. alpha-Lipoic acid formed complexes with silver particles and reduced silver-induced formation of reactive oxygen species, mitochondrial damage and liver toxicity. Our data suggest that nanosilver application in the presence of alpha-lipoic acid is safe and effective in the treatment of pancreatic cancer. Silver nanoparticles (AgNPs) have attracted attention in cancer therapy and might support the treatment of pancreatic ductal adenocarcinoma (PDAC). Silver is in clinical use in wound dressings, catheters, stents and implants. However, the side effects of systemic AgNP treatment due to silver accumulation limit its therapeutic application. We evaluated whether the antioxidant and natural agent alpha-lipoic acid might prevent these side effects. We synthesized AgNPs using an Ionic-Pulser (R) Pro silver generator and determined the concentration by inductively coupled plasma-optical emission spectrometry. The effect of alpha-lipoic acid was examined in four PDAC and two nonmalignant cell lines by MTT, FACS analysis, TEM, xenotransplantation and immunohistochemistry. The viability of PDAC cells was nearly totally abolished by AgNP treatment, whereas nonmalignant cells largely resisted. alpha-Lipoic acid prevented AgNP-induced cytotoxicity in nonmalignant cells but not in PDAC cells, which might be due to the higher sensitivity of malignant cells to silver-induced cytotoxicity. alpha-Lipoic acid protected mitochondria from AgNP-induced damage and led to precipitation of AgNPs. AgNPs reduced the growth of tumor xenografts, and cotreatment with alpha-lipoic acid protected chick embryos from AgNP-induced liver damage. Together, alpha-lipoic acid strongly reduced AgNP-induced side effects without weakening the therapeutic efficacy.

引用

页数：26

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