Mesoporous silica and polymer hybrid nanogels for multistage delivery of an anticancer drug

Effective treatment of cancer has always been a major medical problem. Although some nanoformulations can guide chemotherapeutic drugs to reach the tumor sites, their large size (~ 100 nm) is still the bottleneck for the treatment of solid tumors through deep penetration. In this study, we develop a kind of biodegradable hybrid nanogels to multistage delivery of anticancer drug. The nanogels can effectively encapsulate an anticancer drug (doxorubicin hydrochloride) and accelerate its release under redox and acidic conditions mimicking tumor and intracellular situations as well as controlling its release using a remote heating approach. Furthermore, the nanogels can enter the narrow space between the cells by diminishing their sizes to 40–60 nm drug-carrying mesoporous silica nanoparticles at solid tumor area, eventually entering the tumor cells and functioning in the nucleus. The drug-loaded nanogels present higher intracellular drug accumulation capacity, resulting in a two-fold enhancement in anticancer cytotoxicity as compared to free drug, suggesting their high potential as a good nanoplatform for delivery of therapeutic agents.