In Vitro and In Vivo Anticancer and Genotoxicity Profiles of Green Synthesized and Chemically Synthesized Silver Nanoparticles.

Abstract

Silver nanoparticles were green synthesized (Ag-PTs) employing the crude extract of Padina tetrastromatica, a marine alga, and their anticancer and safety profile were compared with those of chemically synthesized silver nanoparticles (Ag-NPs) by in vitro and in vivo models. Ag-PT exhibited potent cytotoxicity against B16-F10 (IC50 = 3.29), MCF-7 (IC50 = 4.36), HEPG2 (IC50 =3.89), and HeLa (IC50 = 4.97) cancer cell lines, whereas they exhibited lower toxicity on normal CHO-K1 cells (IC50 = 5.16). The potent anticancer activity of Ag-PTs on cancer cells is due to the liberation of ions from the nanoparticles. Increased ion internalization to the cells promotes reactive oxygen species (ROS) production and ultimately leads to cell death. The in vitro anticancer results and in vivo melanoma tumor regression study showed significant inhibition of melanoma tumor growth due to Ag-PT treatment. Ag-PT is involved in the upregulation of the p53 protein and downregulation of Sox-2 along with the Ki-67 protein. The antitumor effects of Ag-PTs may be due to the additional release of ions at a lower pH of the tumor microenvironment than that of the normal tissue. The results of safety investigations of Ag-PT by studying mitotic chromosome aberrations (CAs), micronucleus (MN) induction, and mitotic index (MI) demonstrated Ag-PT to be less genotoxic compared to Ag-NP. The bioefficacy and toxicology outcomes together demonstrated that the green synthesized silver nanoparticles (Ag-PTs) could be explored to develop a biocompatible, therapeutic agent and a vehicle of drug delivery for various biomedical applications.