Preparation of hyaluronic acid-decorated hollow meso-organosilica/poly(methacrylic acid) nanospheres with redox/pH dual responsivity for delivery of curcumin to breast cancer cells

Abstract

Present cancer treatment using chemotherapy is limited owing to serious adverse effects on normal cells. To manage this problem, targeted drug delivery using smart polymeric nanoparticles and/or mesoporous silica nanoparticles can play a key role. In this study, a combination of surfactant-directed sol-gel and seeded precipitation polymerization techniques were designed to synthesize hyaluronic acid-decorated pH and redox dual-stimuli responsive hollow mesoporous organosilica/poly(methacrylic acid) nanospheres for active-targeted delivery of curcumin to breast cancer cells. The obtained nanospheres possess diameter less than 200 nm, high negative zeta potential (−30 mV), and narrow size distribution. The prepared nanospheres exhibited a high entrapment efficiency up to 70 % and drug loading capacity more than 10 % for curcumin. In vitro drug release studies showed that, the cumulative drug release was remarkably restricted under normal physiological media (neutral pH and in the absence of glutathione), while it was accelerated at the simulated tumor tissue conditions (acidic pH and in the presence of glutathione), indicating redox and pH-responsivity of the prepared nanocarrier. In vitro cytotoxicity and apoptosis assays demonstrated that the empty nanospheres have excellent biocompatibility, and curcumin-loaded targeted nanospheres are more cytotoxic against MCF-7 human breast cancer cells compared to the free drug and non-targeted nanospheres.