Wu Jingjing, Liu Yang, Cao Meiwen, Zheng Nannan, Ma Hongchao, Ye Xiandong, Yang Nanyan, Liu Zhihong, Liao Wangjun, Sun Li
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Department of Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), No. 1 East Banshan Road, Gongshu District, Hangzhou, Zhejiang 310022, China.
ACS Appl Mater Interfaces. 2023 Feb 1;15(4):5667-5678. doi: 10.1021/acsami.2c20388. Epub 2023 Jan 18.
Hypoxia, as a main feature of the tumor microenvironment, has greatly limited the efficacy of photodynamic therapy (PDT), as well as its clinical application. Here, a multifunctional composite nanoplatform, the peptide/Ce6/MnO nanocomposite (), has been constructed to alleviate tumor hypoxia and increase the efficacy of PDT using rationally designed peptide fibrils to encapsulate chlorin e6 (Ce6) inside and to mineralize MnO nanoparticles on the surface. As a result, significantly improved the PDT efficacy by increasing reactive oxygen species (ROS) generation, decreasing tumor cell viability, and inhibiting tumor growth and metastasis. Besides, decreased HIF-1α expression and increased immune-activated cell infiltration were also observed in /laser treatment xenograft. Mechanically, (1) Ce6 can induce singlet oxygen (O) generation under laser irradiation to give photodynamic therapy (PDT); (2) MnO can react with HO in situ to supply additional O to alleviate tumor hypoxia; and (3) the released Mn ions can induce a Fenton-like reaction to generate OH for chemical dynamic therapy (CDT). Moreover, /laser treatment also presented with an abscopal effect to block the occurrence of lung metastasis by remolding the pre-metastasis immune microenvironment. With these several aspects working together, the peptide/Ce6/MnO nanoplatform can achieve highly efficient tumor therapy. Such a strategy based on peptide self-assembly provides a promising way to rationally design a cancer-responsive multifunctional nanoplatform for highly efficient combined cancer therapy by alleviating hypoxia and improving the immune microenvironment.
缺氧作为肿瘤微环境的主要特征，极大地限制了光动力疗法（PDT）的疗效及其临床应用。在此，构建了一种多功能复合纳米平台，即肽/Ce6/MnO纳米复合材料（），通过合理设计肽纤维将二氢卟吩e6（Ce6）包裹在内部，并使MnO纳米颗粒在表面矿化，以缓解肿瘤缺氧并提高PDT的疗效。结果，通过增加活性氧（ROS）的产生、降低肿瘤细胞活力以及抑制肿瘤生长和转移，显著提高了PDT疗效。此外，在/激光治疗的异种移植瘤中还观察到缺氧诱导因子-1α（HIF-1α）表达降低和免疫激活细胞浸润增加。从机制上讲，（1）Ce6在激光照射下可诱导单线态氧（O）生成，从而实现光动力疗法（PDT）；（2）MnO可与原位的HO反应以提供额外的O来缓解肿瘤缺氧；（3）释放的Mn离子可诱导类芬顿反应生成羟基自由基（OH）用于化学动力疗法（CDT）。此外，/激光治疗还呈现出远隔效应，通过重塑转移前免疫微环境来阻止肺转移的发生。通过这几个方面的协同作用，肽/Ce6/MnO纳米平台可实现高效的肿瘤治疗。这种基于肽自组装的策略为合理设计一种癌症响应性多功能纳米平台提供了一条有前景的途径，通过缓解缺氧和改善免疫微环境来实现高效的联合癌症治疗。
