Bleach etches nanosilver: HOCl-responsive drug delivery system to target leukemic cells

Abstract

In addition to their well-known antibacterial property, silver nanoparticles (Ag NPs) have also been highlighted as anti-leukemic agents; however, the underlying mechanism responsible for inhibiting the growth of hematopoietic cancer cells is so far poorly understood. In previous reports, Ag NP-induced oxidative stress was implicated for therapeutic efficacy but the excessive production of ROS in several hematopoietic malignant cells, which can potentially induce the dissolution of Ag NPs, was not taken into consideration. In this study we proposed Ag NP dissolution, in response to increased oxidative stress in leukemic cells, as the most probable mechanism for their anticancer activity. Hypochlorous acid-mediated dissolution of therapeutically active and ultrasmall (<5 nm) Ag NPs was also exploited to develop an oxidant responsive combinatorial drug delivery system. When Ag-capped and anticancer drug loaded pores of mesoporous silica were exposed to HOCl, the ready disintegration of Ag NPs resulted in a controlled release of drug molecules. The drug release profile and growth inhibition of myeloperoxidase positive (MOLM-13) leukemic cells support the role of the oxidant in the dissolution of Ag NPs. Besides combinational chemotherapy, the current study also provides us with an opportunity to investigate the interaction of Ag NPs with biorelevant oxidants.