Tumor-responsive nanomedicines for cancer therapy: design principles and therapeutic advances

Abstract Tumor microenvironment (TME)-responsive nanomedicines have emerged as a promising precision therapeutic strategy in cancer treatment. By incorporating stimuli-responsive properties, these nanomedicines can achieve targeted delivery and controlled release at tumor sites, thereby enhancing therapeutic efficacy while minimizing side effects. This review provides a comprehensive overview of the latest advancements in TME-responsive nanomedicines for cancer immunotherapy, covering various stimulus-responsive mechanisms (such as pH, reactive oxygen species, hypoxia, enzymes, and ATP) and their applications in improving immune efficacy and reducing immune-related adverse effects. In addition to discusses the key challenges associated with the clinical translation of these nanomedicines and proposes future research directions. This work aims to offer a theoretical foundation and design reference for the further development and application of tumor-responsive nanomedicines.