Li Cheng-Ao, Nan Junjie, Ye Qingxuan, Zheng Bingzhu, Dai Xiaomeng, Li Jingya, Wang Feng, Ma Huimin, Cheng Yu, Ruan Jian, Fang Weijia, Zhao Peng, Deng Renren, Cen Dong
State Key Laboratory of Silicon and Advanced Semiconductor Materials, Institute for Composites Science Innovation, School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310058, China.
Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Adv Sci (Weinh). 2025 Sep;12(33):e05525. doi: 10.1002/advs.202505525. Epub 2025 Jun 9.
Pro-inflammatory photodynamic therapy (PDT) holds immense potential to ignite robust and long-lasting systemic anti-tumor immune responses. However, the limited penetration depth of conventional ultra violet (UV)-visible irradiation and the tumor hypoxia microenvironment significantly constrain the efficacy of immune-regulatory PDT. Here, a mitochondria-targeting enhanced nanoplatform (NZ) is reported, activated by near-infrared (NIR) light-driven PDT, to address these challenges and amplify systemic anti-tumor immunity. This nanoplatform employs an interfacial lanthanide-organic triplet photosensation mechanism to realize localized oxidative damage of oxygen-rich mitochondria under NIR irradiation. Simultaneously, the exacerbated hypoxia induced by PDT activates a TH302 prodrug, resulting in cell cycle arrest in highly proliferative tumor cells. These combined effects trigger immunogenic cell death (ICD), releasing damage-associated molecular patterns (DAMPs) to activate immune responses. This approach demonstrates significantly enhanced tumor ablation in deep-seated lesions in orthotopic liver tumor models and induces long-term anti-tumor immune memory. Moreover, the NIR-PDT-induced immune activation markedly improves the immune checkpoint blockade (ICB) therapy efficacy. This strategy offers a robust modality for immune activation in cancer therapy, paving the way for effective treatment of deep-seated tumors and preventing recurrence.
促炎性光动力疗法（PDT）具有引发强大且持久的全身抗肿瘤免疫反应的巨大潜力。然而，传统紫外（UV）-可见光照射的穿透深度有限以及肿瘤缺氧微环境显著限制了免疫调节性PDT的疗效。在此，报道了一种由近红外（NIR）光驱动的PDT激活的线粒体靶向增强纳米平台（NZ），以应对这些挑战并增强全身抗肿瘤免疫力。该纳米平台采用界面镧系元素-有机三线态光敏化机制，在近红外照射下实现富氧线粒体的局部氧化损伤。同时，PDT诱导的缺氧加剧激活了TH302前药，导致高度增殖的肿瘤细胞发生细胞周期阻滞。这些联合效应触发免疫原性细胞死亡（ICD），释放损伤相关分子模式（DAMPs）以激活免疫反应。该方法在原位肝肿瘤模型的深部病变中显示出显著增强的肿瘤消融效果，并诱导长期抗肿瘤免疫记忆。此外，近红外光动力疗法诱导的免疫激活显著提高了免疫检查点阻断（ICB）治疗的疗效。该策略为癌症治疗中的免疫激活提供了一种强大的方式，为深部肿瘤的有效治疗和预防复发铺平了道路。
