Tumor-Microenvironment-Responsive Nanomedicine for Enhanced Cancer Immunotherapy

The past decades have witnessed great progress in cancer immunotherapy, which has profoundly revolutionized oncology, whereas low patient response rates and potential immune-related adverse events remain major clinical challenges. With the advantages of controlled delivery and modular flexibility, cancer nanomedicine has offered opportunities to strengthen antitumor immune responses and to sensitize tumor to immunotherapy. Furthermore, tumor-microenvironment (TME)-responsive nanomedicine has been demonstrated to achieve specific and localized amplification of the immune response in tumor tissue in a safe and effective manner, increasing patient response rates to immunotherapy and reducing the immune-related side effects simultaneously. Here, the recent progress of TME-responsive nanomedicine for cancer immunotherapy is summarized, which responds to the signals in the TME, such as weak acidity, reductive environment, high-level reactive oxygen species, hypoxia, overexpressed enzymes, and high-level adenosine triphosphate. Moreover, the potential to combine nanomedicine-based therapy and immunotherapeutic strategies to overcome each step of the cancer-immunity cycle and to enhance antitumor effects is discussed. Finally, existing challenges and further perspectives in this rising field with the hope for improved development of clinical applications are discussed.