Bioengineering of green-synthesized TAT peptide-functionalized silver nanoparticles for apoptotic cell-death mediated therapy of breast adenocarcinoma

Abstract

Green synthesized silver-nanomaterial has exhibited significant advantages as cancer therapeutics due to their exclusive characteristics that cause inducing various forms of cell death; particularly, they have attracted much attention in the treatment of breast cancer. More specifically, the exploration of silver nanoparticles (SNPs) in investigation of cancer treatment is of booming interest due to the opportunity to customize the physicochemical properties of NPs, to enhance their biocompatibility and interactive potentials through surface functionalization. In the present study, first SNPs were fabricated from Staphylococcus aureus cell-free extract, and then the surface modification was executed by conjugating trans-activator of transcription (TAT) peptide, which is a cell-penetrating peptide to enhance the induction of apoptosis in the breast adenocarcinoma cells. The physicochemical characteristics of both virgin SNPs and TAT peptide conjugated SNPs (cSNPs) were evaluated using UV–vis spectrophotometer, FTIR, SEM-EDX, TGA, DSC, and TEM. FTIR analysis revealed the involvement of amide and amines in SNPs synthesis. The SEM analysis confirmed the spherical shape of SNPs, while EDX showed the elemental nature of silver. TGA determined the protein loss at second weight loss of nearly 45%, and DSC confirmed the endothermic phase transition of both SNPs and cSNPs. Moreover, TEM revealed the particle size of about 26.94 nm and 21.94 nm for SNPs and cSNPs, respectively. In regard to the cancer therapeutic potentials of NPs, the cSNPs exhibited potential cytotoxic activity of IC50 (30.05 μg/mL) against MDA-MB-231 breast cancer cells compared to SNPs that induced apoptosis by enhancing the upregulation of p53 protein expression. Internment flow cytometry data confirmed the productions of ROS radicals in the treated cells of the MDA-MB-231 cells. Overall, our study shows that the surface functionalization of SNPs by employing potential inhouse human-derived peptides could be a new and promising approach in cancer therapy.