Synergistic Cytotoxic Effects of Doxorubicin Loaded Silver, Gold and Zinc Oxide Nanoparticles in HepG2 Liver Cancer Cells

Hepatocellular carcinoma is the most prevalent cancer worldwide and has a high mortality rate. Many chemotherapeutic agents have been used for treatment; however, their success is limited because of the lack of site-specific targeted drug delivery. Thus, the nanoparticle-based targeted drug delivery approach can reduce the challenges associated with conventional chemotherapy. This study evaluated the synergistic potential of gold (Au), silver (Ag), and zinc oxide (ZnO) nanoparticles (NPs) loaded with doxorubicin (DOX) in HepG2 cancer cells. DOX loaded onto Au, Ag, and ZnO NPs via surface adsorption. The efficiency of in vitro controlled release was investigated under optimum pH and release time conditions. The synergistic effect of DOX-loaded NPs on cell proliferation was evaluated using cytotoxicity assay. The gene expression levels of regulatory proteins were estimated using RT-PCR. The binding energy between Ag: DOX and the anticancer proteins was investigated using molecular docking approach. The drug loading and release efficiencies of Ag: DOX, Au: DOX, and ZnO: DOX were 81.94%, 85.27%, and 93.25% and 96.2%, 88.4%, and 82.4%, respectively, revealing a sustained release pattern for Ag: DOX. Ag: DOX showed enhanced cytotoxicity with a 48.8% viability rate, suggesting a synergistic effect. Upregulation of p53 and caspase9 and downregulation of BcL2 and AKT were observed. Docking studies validated the interaction between Ag: DOX and regulatory proteins. The results suggest that Ag: DOX is a suitable and efficient nanoconjugate for DOX delivery with synergistic effect with potential to be used for the treatment of hepatocellular carcinoma.