Recent Advances in Intelligent Polyphenol-Based Hydrogels: Engineering Strategies for Tumor Microenvironment Modulation

The tumor microenvironment (TME), a complex milieu characterized by acidity, high redox levels, hypoxia and inflammation, supports tumor progression and contributes to therapeutic failure. Moreover, TME imposes immunosuppression, marked by the infiltration of numerous immunosuppressive cells, which impairs the efficacy of immunotherapy. Polyphenol-based hydrogels (PBHs) have emerged as biocompatible materials for in situ TME modulation, owing to their specific cross-linking structures that endow them with unique features, including intrinsic adhesiveness, antioxidant, anti-inflammatory and immunomodulatory properties. Here, the typical types and representative engineering strategies of intelligent PBHs are first introduced, which are responsive to endogenous signals within TME including pH, reactive oxygen species and glutathione. Then their unique biological properties are summarized. Subsequently, their advances in TME modulation are highlighted, such as intelligent targeted drug delivery and release, reactive oxygen species scavenging, anti-inflammatory effects, and immunosuppressive TME remodeling. Finally, we discuss the challenges and development prospects of PBHs for advanced cancer therapy.