Fan Yuan-Yuan, Wu Hong, Xu Chuan
Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
Pharmaceutics. 2025 Jul 5;17(7):886. doi: 10.3390/pharmaceutics17070886.
Despite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained in solid tumors due to the immunosuppressive tumor microenvironment (TME). Reactive oxygen species (ROS), which exhibit dual regulatory roles in the TME by regulating immunogenic cell death (ICD) and reprogramming immune cell functionality, have emerged as a pivotal therapeutic target. Nano-enabled drug delivery systems present distinct advantages for TME modulation due to their structural versatility, tumor-specific targeting precision, and spatiotemporally controlled drug release. In particular, ROS-responsive nanoplatforms demonstrate multifaceted immunomodulatory potential by synergistically restoring ICD and remodeling immunosuppressive immune cell phenotypes within the TME. These platforms further amplify the therapeutic outcomes of conventional modalities including chemotherapy, radiotherapy, and photodynamic therapy (PDT) through ROS-mediated sensitization mechanisms. This review comprehensively examines recent breakthroughs in ROS-responsive nanosystems for antitumor immunotherapy, emphasizing their mechanistic interplay with TME components and clinical translation potential. Herein, we provide a framework for developing integrated therapeutic strategies to overcome the current limitations in cancer immunotherapy.
尽管癌症免疫疗法取得了显著进展，但其临床疗效在实体瘤中仍受到免疫抑制性肿瘤微环境（TME）的限制。活性氧（ROS）通过调节免疫原性细胞死亡（ICD）和重编程免疫细胞功能在TME中发挥双重调节作用，已成为关键的治疗靶点。基于纳米的药物递送系统因其结构的多功能性、肿瘤特异性靶向精度和时空可控的药物释放，在TME调节方面具有独特优势。特别是，ROS响应性纳米平台通过协同恢复ICD和重塑TME内免疫抑制性免疫细胞表型，展现出多方面的免疫调节潜力。这些平台通过ROS介导的敏化机制进一步放大了包括化疗、放疗和光动力疗法（PDT）在内的传统治疗方式的治疗效果。本综述全面审视了用于抗肿瘤免疫疗法的ROS响应性纳米系统的最新突破，强调了它们与TME成分的机制相互作用以及临床转化潜力。在此，我们提供了一个开发综合治疗策略的框架，以克服当前癌症免疫疗法中的局限性。
