Doxorubicin functionalized metallic nanoparticles for anticancer and antibacterial applications

Abstract

In this study, we used Doxorubicin, an FDA approved drug possessing anticancer and antibacterial activity, as a model drug to functionalize sugar ligand synthesized silver/gold bimetallic nanoparticles (Ag/AuNPs) to test simultaneous antibacterial and anticancer activities under in vitro conditions. DU-145 prostate cancer cells were used as the main target while T98G glioblastoma and MDA-MB-231 breast cancer cell lines were used for selectivity test, and HEK-293 epithelial cell line was used as non-cancerous cells to test toxicity of these formulations. Three Ag/AuNP and corresponding Doxorubicin (D) functionalized ones and free Doxorubicin were tested for these four cell lines. Plain Ag/AuNP showed the highest toxicities on HEK-293 cell lines while DU-145 cell line showed the greatest vulnerability for Ag/AuNP-D formulations. However, DU-145 cells showed the lowest susceptibility for free Doxorubicin at all the tested concentrations. The antiproliferative activity was not dose dependent while an inverse relationship was obtained for a certain concentration range. Two Doxorubicin functionalized gold nanoparticles (AuNP-D) were then synthesized and applied on DU-145 cells. Interestingly, a better anticancer activity was obtained even at the minimum applied concentration (1.8 x 10-5 mu g/mL D). Antibacterial activities of these formulations were also tested for multidrug-resistant gram (-) and gram (+) bacterial species. Depending on the sugar ligand chemistry, antibacterial activity of Doxorubicin functionalized Ag/AuNPs showed a better performance in comparison to the plain Ag/AuNPs and vice-versa. Based on the results, it can be claimed that selective or semi-selective formulations targeting cancer cells and bacterial species as anti-neutropenia formulations can be developed using carbohydrate derivatives synthesized metallic nanoparticles as drug delivery agents.