Here, we demonstrated a pH-responsive nanocluster based on ZnO quantum dots (QDs) and investigated its potential in drug delivery with tumor-specific accumulation. The nanoclusters were composed of small single ZnO QDs by cross-linking dicarboxyl-terminated poly(ethylene glycol) (PEG), showing high stability and biocompatibility in physiological fluids. The clustered ZnO QDs were capable of loading a large quantity of doxorubicin (DOX) via complexation and covalent interactions. After cellular uptake, the drug was efficiently released because the carrier was completely dissolved; the metal-drug complex was disassembled in response to decreasing pH in the endosomes within tumor cells. Moreover, the viability of cancer cells was significantly decreased because the ZnO QDs exhibited cytotoxicity postdissolution and preferentially killed cancerous cells compared to normal cells. Furthermore, this pH-responsive PEG-cZnO QDs cluster system may be capable of tumor homing while circulating in the blood via the enhanced permeability and retention (EPR) effect.
Keywords: EPR effect; ZnO cluster; doxorubicin; pH-responsive; tumor homing.