pH-Responsive Biomaterials for Tumor-Targeted Drug Delivery and Controlled Degradation

Cancer has become a major threat to human health, and its treatment is still hampered by challenges such as poor drug targeting and significant toxic side effects. In recent years, the acidic nature of the tumor microenvironment (TME) has offered new avenues for tumor-targeted therapy, and pH-responsive materials have garnered considerable attention for their selective release capabilities. A variety of pH-responsive drug delivery systems have been developed, including polymeric micelles, hydrogels, liposomes, and acid-labile chemical bond conjugation systems, designed to ensure stability in the bloodstream and specific drug release within the acidic TME. However, limitations remain, such as insufficient spatiotemporal precision in drug release and restricted delivery efficiency. This review systematically summarizes the research advancements in pH-responsive materials for tumor-targeted therapy, analyzes the acidic basis of the TME and its implications for material design, encompassing response mechanisms, commonly used materials, structural designs, and multiple response strategies. Furthermore, targeting mechanisms, controlled release platforms, personalized designs, and theranostic integration strategies in precision drug delivery are discussed. A detailed overview of controllable degradation is also presented, ranging from degradation mechanisms to regulation strategies, highlighting the importance of material metabolic safety in clinical translation. This study provides a reference for the structural design and functional integration of future pH-responsive intelligent materials.