Huang Qianqian, Tong Fan, Chen Jiantao, Kayumov Muzaffar, Lv Yue, Shi Yajun, Ye Bengui, Gao Huile
Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Pharmacy College, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Key Laboratory of Leather Chemistry and Engineering (Ministry of Education), West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
Adv Sci (Weinh). 2025 Oct;12(40):e13567. doi: 10.1002/advs.202513567. Epub 2025 Sep 12.
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.
免疫疗法已成为肿瘤学中一种变革性的范式，但其临床疗效仍受到免疫抑制性肿瘤微环境以及现有疗法时空控制不足的限制，导致患者反应率不理想且频繁出现免疫相关不良事件。能够精确调节免疫治疗药物递送动力学的刺激响应性生物材料，已被证实是实现靶向免疫调节的有力策略。本综述系统地阐述了利用肿瘤微环境（TME）动态特征的TME响应性纳米材料的创新设计框架。通过详细剖析癌症-免疫循环障碍，包括受损的抗原呈递、T细胞启动/激活受损以及效应器功能缺陷，强调了下一代递送平台的突破性进展，这些进展在关键时刻重新激发抗肿瘤免疫力。此外，还评估了TME响应性纳米材料的临床前验证和临床转化挑战。基于当前免疫疗法的趋势，本综述还确定了关键的转化决定因素，旨在弥合精准癌症免疫疗法从 bench 到 bedside 的差距。
