Liu Min, Tang Yiwen, Yan Mijia, Zhang Jiale, Chen Hangrong, Zhang Qiuhong
School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-Lane Xiangshan, Hangzhou, 310024, China; State Key Laboratory of High-Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai, 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-Lane Xiangshan, Hangzhou, 310024, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China.
Biomaterials. 2025 Jul;318:123187. doi: 10.1016/j.biomaterials.2025.123187. Epub 2025 Feb 13.
Cancer thermal immunotherapeutic strategy has garnered tremendous attention in nanomedicine frontier. Photothermal therapy (PTT) within the second near-infrared (NIR-II) window is popular hyperthermia technique, but the effect of NIR-II PTT on antitumor immunity remains extensive exploration. Here, we first reveal the inflammatory immunosuppressive tumor microenvironment (TME) characterized by high-influx of myeloid-derived suppressor cells (MDSCs) following NIR-II PTT. For this issue, we develop biomineralized copper sulfide nanoparticles (BCS NPs) as NIR-II photothermal agents (PTAs), and found for the first time that they are superior electron-donor antioxidants with pronounced anti-inflammatory activities. Impressively, the excessive inflammation triggered by BCS NPs-mediated NIR-II PTT can be self-alleviated to minimize the high-influx of MDSCs, and the immunosuppression-related reactive oxygen species produced by MDSCs can also be self-scavenged. Such reprogramming of TME facilitates the activation of systemic adaptive antitumor immunity and the strengthened tumour-infiltrating of cytotoxic T lymphocytes, thereby realizing self-reinforcing immunotherapy synergy with cancer NIR-II PTT. More importantly, a robust abscopal effect against distant tumors is also observed in bilateral tumor models. This work provides the first example to underscore the potential of PTAs with antioxidant and anti-inflammatory functions as innovative thermal immuno-nanomedicines.
癌症热免疫治疗策略在纳米医学前沿领域引起了极大关注。近红外二区（NIR-II）窗口内的光热疗法（PTT）是一种常用的热疗技术，但NIR-II PTT对抗肿瘤免疫的影响仍有待深入探索。在此，我们首次揭示了NIR-II PTT后以髓源性抑制细胞（MDSCs）大量涌入为特征的炎性免疫抑制肿瘤微环境（TME）。针对这一问题，我们开发了生物矿化硫化铜纳米颗粒（BCS NPs）作为NIR-II光热剂（PTAs），并首次发现它们是具有显著抗炎活性的优质电子供体抗氧化剂。令人印象深刻的是，BCS NPs介导的NIR-II PTT引发的过度炎症可自我缓解，以尽量减少MDSCs的大量涌入，并且MDSCs产生的与免疫抑制相关的活性氧也可被自我清除。这种TME的重编程促进了全身适应性抗肿瘤免疫的激活以及细胞毒性T淋巴细胞在肿瘤中的浸润增强，从而实现了与癌症NIR-II PTT的自我强化免疫治疗协同作用。更重要的是，在双侧肿瘤模型中也观察到了对远处肿瘤的强大远隔效应。这项工作首次例证了具有抗氧化和抗炎功能的PTAs作为创新热免疫纳米药物的潜力。
