Ternary-responsive magnetic nanocarriers for targeted delivery of thiol-containing anticancer drugs

Abstract

Cancer is currently the second leading cause of death in the world and one of the most serious challenges in medical therapy. Targeted nanocarrier systems potentially propose a solution to the severe side effects associated with direct drug delivery to the tumor cells (conventional chemotherapy). A novel multi (magnetic, thermo, pH and redox) responsive drug nanocarrier was successfully prepared through the grafting of poly(N-isopropylacrylamide-co-maleic anhydride-g-S-S-Py), fully characterized by various techniques and subsequently used for loading and targeted delivery of 6-mercaptopurine (6MP), a thiol containing anticancer drug. The in vitro drug release behavior of 6MP over 24 h was investigated in the presence of GSH (10 mM and 2 mu M for simulating intra and extracellular conditions, respectively) under physiologic (37 degrees C, pH 7.4) and simulated cancerous tissue (40 degrees C, pH 5.3) conditions. The thermo, pH and redox responsive 6MP release ability of the developed nanocarriers was proved through the in vitro drug release study. The cell cytotoxicity study on the Raji (Burkitt lymphoma) cell line indicated efficient performance of multi-responsive 6MP-loaded nanocarriers. It was concluded that the newly developed multi-responsive nanocarriers have promising potential for targeting of thiol containing anticancer drugs to the tumor tissues.