Tumor Microenvironment Responsive Mesoporous Silica Nanoparticles for Dual Delivery of Doxorubicin and Chemodynamic Therapy (CDT) Agent

Chemodynamic therapy is a newly antitumor strategy triggered by transition metal as chemodynamic agent via the in-situ catalytic Fenton reaction. Herein, we engineer a smart nanocarrier activated by tumor microenvironment specific weak acidic pH and high glutathione condition for chemo/chemodynamic process. This unique architecture orderly consists of mesosilica encapsulated doxorubicin, self-polymerization of polydopamine Fe3+ clathrate, further bonding the targeting polymer MnO2 disguised albumin-folic acid. Polydopamine and albumin as intelligent nanovalves shields doxorubicin from premature leaking. Folic acid improves the targeted capability to folate receptor (FR) overexpressed cancer cells. After the nanocarrier intake to tumor cells, the nanocarrier`s nanovalves could be first biodegraded by native glutathione and pH, enabling on-demand anticancer drug escape, also release and generates Fe3+ and Mn2+ (reduced by MnO2 via glutathione depletion). Subsequently, the ions interact with H2O2 generating high toxic hydroxyl radicals (·OH) via Fenton-like reaction to enhance the anticancer cell efficacy. The result is proving that the designed nanocarrier more likely devours into FR-positive cancer cells and illustrates a high intracellular ·OH generation leading to desired specific killing efficacy. We believe this innovative strategy will exhibits a new avenue for the potential of accurate chemo/chemodynamic co-therapy in cancer cells.