Tunable synthesis of pH-responsive biodegradable ZnO nanospheres assembled from ultrasmall particles for cancer chemotherapy

The biodegradable nanoparticles hold tremendous potential in the field of nanomedicine because of the negligible toxicity concerns in healthy tissues/organs. We reported a simple route for the synthesis of pH-responsive biodegradable ZnO nanospheres (ZnO NSs) assembled from ultrasmall particles (sizes ranging from 4 to 8 nm, average 6 nm) with a suitable size. The nanoplatform could be responsively decomposed into small fragments under the weak acid environment to meet the requirement for pH-stimulus drug release and in favor of the biodegradation. The confocal laser scanning microscopy (CLSM) studies showed that the ZnO NSs could be efficiently internalized by cancer cells, and the loaded doxorubicin (DOX) in the NSs could be successfully released under acidic intracellular environment. Notably, the cell viabilities of DOX-loaded NSs with different sizes towards HepG-2 and HeLa cells for different incubation time were investigated, which exhibited dose-dependent and time-dependent effects. Furthermore, in vivo experiments showed that the DOX-loaded NSs displayed a significant antitumor effect (79% average inhibition rate relative to the control group) without distinct side effects. All in all the designed NSs as drug delivery systems not only achieved the excellent cancer chemotherapy but also could be rapidly decomposed or metabolized to reduce their toxicity.