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

Abstract

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 α-lipoic acid might prevent these side effects. We synthesized AgNPs using an Ionic-Pulser® Pro silver generator and determined the concentration by inductively coupled plasma–optical emission spectrometry. The effect of α-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. α-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. α-Lipoic acid protected mitochondria from AgNP-induced damage and led to precipitation of AgNPs. AgNPs reduced the growth of tumor xenografts, and cotreatment with α-lipoic acid protected chick embryos from AgNP-induced liver damage. Together, α-lipoic acid strongly reduced AgNP-induced side effects without weakening the therapeutic efficacy.

Evaluation of the protective roles of alpha-lipoic acid supplementation on nanomaterial-induced toxicity: A meta-analysis of in vitro and in vivo studies

“…Consequently, three studies were further eliminated because of the following reasons: data unavailable (only the mean provided; n = 1) ( 31 ); data could not be integrated with other studies (percentage relative controls provided, not specific concentration for outcomes; n = 1) ( 18 ); ALA modified in NPs and thus only ALA-NP dose was provided, not ALA dose as other studies ( n = 1) ( 32 ). Eventually, eight in vivo ( 11 , 17 , 19 , 26 , 27 , 33 – 35 ) and four in vitro ( 20 , 21 , 36 , 37 ) studies were included in our meta-analysis.…”

“…In addition to anti-oxidant and anti-inflammatory effects, ALA was considered as a metal chelator to prevent metal ion-induced toxicity ( 19 , 20 , 33 , 35 , 37 ). Hereby, in this study, we also analyzed the metal ions of NPs in animals and cells.…”