Tumor Microenvironment-Responsive Nanomedicines for Potentiating Cancer Immunotherapy

Immunotherapy has emerged as a transformative paradigm in oncology, yet its clinical efficacy remains constrained by the immunosuppressive tumor microenvironment and inadequate spatiotemporal control of existing modalities, resulting in suboptimal patient response rates and frequent immune-related adverse events. Stimuli-responsive biomaterials, capable of precise modulation over the delivery kinetics of immunotherapeutic agents, are validated as powerful strategies for achieving targeted immunomodulation. This review systematically delineates innovative design frameworks for tumor microenvironment (TME)-responsive nanomaterials leveraging dynamic TME features. Through detailed dissection of cancer-immunity cycle barriers, including spanning impaired antigen presentation, compromised T cell priming/activation, and defective effector function, breakthrough advances in next-generation delivery platforms are highlighted that reignite antitumor immunity at a critical juncture. Furthermore, preclinical validation and clinical translation challenges of TME-responsive nanomaterials are evaluated. Building upon current immunotherapy trends, this review also identifies critical translational determinants, with the aim of bridging the bench-to-bedside gap in precision cancer immunotherapy.