Chitosan gold nanoparticles induce cell death in HeLa and MCF-7 cells through reactive oxygen species production

Abstract

BackgroundNanotechnology has gained important interest, especially in the development of new therapies; the application of gold nanoparticles (AuNPs) in the treatment and detection of diseases is a growing trend in this field. As cancer represents a serious health problem around the world, AuNPs are studied as potential drugs or drug carriers for anticancer agents. Recent studies show that AuNPs stabilized with chitosan (CH) possess interesting biological activities, including potential antitumor effects that could be selective to cancer cells.Materials and methodsIn this study, we synthesized sodium citrate-AuNPs and CH-capped AuNPs of 3–10 nm, and analyzed their cytotoxicity in cervical (HeLa) and breast (MCF-7) cancer cells, and in peripheral blood mononuclear cells (PBMCs). Then, we evaluated the clonogenic potential, cell cycle, nuclear alterations, caspase dependence, and reactive oxygen species (ROS) production in HeLa and MCF-7 cells after chitosan gold nanoparticles (CH-AuNPs) exposure.ResultsOur data showed that CH-AuNPs are cytotoxic in a dose-dependent manner in the cancer cell lines tested, while they induce low cytotoxicity in PBMCs. Sodium citrate gold nanoparticles did not show cytotoxic effects. In both HeLa and MCF-7 cell lines, CH-AuNPs inhibit clonogenic potential without inducing cell cycle arrest or nuclear alterations. The cell death mechanism is specific for the type of cancer cell line tested, as it depends on caspase activation in HeLa cells, whereas it is caspase independent in MCF-7 cells. In all cases, ROS production is mandatory for cell death induction by CH-AuNPs, as ROS inhibition with N-acetyl cysteine inhibits cell death.ConclusionOur results show that CH-AuNPs are selective for HeLa and MCF-7 cancer cells, rather than normal PBMCs, and that ROS production seems to be a conserved feature of the cell death mechanism induced by CH-AuNPs. These results improve the knowledge of CH-AuNPs and open the way to the design of new pharmacological strategies using these agents against cancer.

Synthesis of Gold Nanoparticles Using Citrus macroptera Fruit Extract: Anti‐Biofilm and Anticancer Activity

“…Thus, the cytotoxic values are greatly varied with the surface chemistry of particles and the type of cells used for the study. Though our preliminary findings are promising but detail investigation is required to find the satisfactory reason for such low concentration cytotoxicity, which is superior or comparable with the reported results ,…”

“…The Cajanuscajan dried seed extract coated AuNPs showed IC50 value at 6 g/ml for 24 h exposure against HepG2 . On the other hand the IC50 value of Chitosan stabilized AuNPs was reported to be 75 ng/ml in 24 h exposure against MCF 7 cell lines . Tannic acid stabilized gold nanosphere reported to have IC50 value 20ng/ml .…”

Antioxidant Properties and Redox-Modulating Activity of Chitosan and Its Derivatives: Biomaterials with Application in Cancer Therapy

“…The experimental results demonstrated that inhibition of ROS production with N-acetyl cysteine leads to inhibition of cell death. 78 Zheng et al investigated the effect of chitosancopper complexes on tumor cell lines 293 and HeLa and normal lung fibroblast cell line HLP. After 48 h of incubation time, cell proliferation was investigated and the results indicated that chitosan-copper complexes selectively inhibited HeLa and 293 tumor cell line proliferation, but there was no inhibition in the growth of HLF.…”

Virucidal Activity of Gold Nanoparticles Synthesized by Green Chemistry Using Garlic Extract

“…The cytotoxicity concentration 50% (CC 50 ) was determined at 141.75 µg/mL for AuNPs-As and 231.74 µg/mL for HAuCl 4 . We also performed a viability assay using gold nanoparticles synthesized by the technique previously reported by Martínez-Torres et al [12] and using chitosan as reducing agent (AuNPs-Chi) to compare the effect of both techniques [13]. This synthesis showed a cytotoxicity of 68.86% at a concentration of 10 µg/mL, which is higher than that of AuNPs-As.…”