pH-Responsive drug delivery system for tumor therapy.

Cancer, as a leading cause of mortality globally, poses significant treatment challenges, including inadequate tumor targeting, severe systemic toxicity, and multidrug resistance. The advent of nanomedicine delivery systems (NDDS) in recent years has led to novel approaches for enhancing drug targeting and mitigating adverse reactions. Among them, pH-responsive NDDS exploit pH gradients in the tumor microenvironment to enable programmed drug release and improved tumor accumulation, thereby enhancing therapeutic efficacy. This article systematically reviews the design strategies, working mechanisms, and application prospects of pH-responsive NDDS in cancer therapy. Firstly, based on the chemical structure of materials, the design of pH-responsive materials through protonation mechanisms and acid-sensitive chemical bonds is introduced. Second, we focus on reviewing how pH responsiveness enhanced the physicochemical properties and biological regulation functions of different categories of NDDS. Then, an overview of the multi-responsive NDDS based on pH response, with a particular emphasis on the significance of pH-responsive design. Finally, we summarize the advantages and limitations of pH-responsive NDDS and offer insights into the future development of pH-responsive materials in the context of evolving nanomaterial science.