ZnO-incorporated alginate assemblies: Tunable pH-responsiveness and improved drug delivery for cancer therapy

Delivering drugs selectively to tumor tissues is a significant challenge in cancer therapy, and pH-responsive polymeric assemblies have shown great potential in achieving this goal. In this study, we developed a pH-responsive alginate-based assemblies, called (amine-modified ZnO)-oxidized alginate-PEG ((ZnO-N)-OAl-PEG), for selective drug delivery in cancer treatment. The incorporation of ZnO-N nanoparticles into the alginate-based assemblies enables pH-responsiveness and maintains stability under physiological conditions. At an acidic pH, (ZnO-N)-OAl-PEG disassembles due to the conversion of ZnO to Zn²⁺, which triggers the unloading of doxorubicin (DOX) from the imine bond between DOX and alginate. This unloading results in the death of cancer cells and inhibition of tumor growth. The anticancer efficacy of (DOX/ZnO-N)-OAl-PEG was demonstrated in vitro and in vivo, providing promising prospects for cancer treatment based on ZnO-induced pH-responsiveness. These findings may also inspire the development of advanced drug delivery systems (DDSs) for cancer therapy.