A selective toxicity of Pt-coated Au nanoparticles in cancerous MCF-7 cells over non-cancerous HUVE cells

Abstract

Objectives: Nitric oxide (NO) and NO-generated reactive nitrogen species (RNS) in conjunction with reactive oxygen species (ROS) have received attention for their potential in oxidative stress-based cancer therapy. Here, we report commercially obtained Pt-coated Au nanoparticles (Pt-Au NPs; 27 ± 20 nm) higher uptake and cytotoxicity in human breast cancer MCF-7 cells as compared to a non-cancerous human cell (HUVE). Methods: Cytotoxicity was evaluated by MTT bioassay followed by measurement of ROS (by DCFH-DA probe) and NO (by DAR-2 probe) in live cells. Membrane integrity was evaluated by measuring lipid peroxidation by live cell dye BODIPY fluorescence, TBARS absorbance, and LDH release. Ubiquitous antioxidant GSH was also measured followed by changes in MMP status by live cell dye JC-1. Mode of cell death was determined by triple staining (Hoechst/annexin V/PI triple staining), and caspase 9 and 3 activities in cancerous MCF-7 and non-cancerous HUVE cell lines. Results: MCF-7 cells exhibited a 63 ± 5 % higher tendency of Pt-Au NPs uptake in comparison to HUVE cells. Accordingly, IC50 of Pt-Au NPs came out to be 0.48 ± 0.09 µM in MCF-7 cells and 0.93 ± 0.11 µM in non-cancerous HUVE cells. Therefore, the cytotoxic potential of NPs in MCF-7 cells was almost 1.9-fold higher than in HUVE cells indicating cancer cells are significantly more susceptible to death than HUVE cells with a normal tissue origin. NPs caused a significant induction in oxidative stress and loss in MMP in the two cells. Conclusion: We realize two major facts from this study that goes in the favor of anticancer potential of Pt-Au NPs. The first reason is the high internalization of NPs in MCF-7 cells as compared to that in HUVE cells. The second reason is that HUVE cells were found not as expressive for NO as were MCF-7 cells.

Keywords

• Cancer cells
• Normal cells
• Nitric oxide
• Apoptosis
• Necrosis
• Anticancer