Yang Zebin, Luo Yu, Yu Huizhu, Liang Kaicheng, Wang Miao, Wang Qigang, Yin Bo, Chen Hangrong
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Dingxi Road 1295, Shanghai, 200050, P. R. China.
School of Chemical Science and Engineering, Tongji University, Siping Road 1239, Shanghai, 200092, P. R. China.
Adv Mater. 2022 Mar;34(11):e2108908. doi: 10.1002/adma.202108908. Epub 2022 Feb 7.
The immunosuppressive tumor microenvironment (TME) always causes poor antitumor immune efficacy, prone to relapse and metastasis. Herein, novel poly(vinylpyrrolidone) (PVP) modified BiFeO /Bi WO (BFO/BWO) with a p-n type heterojunction is constructed for reshaping the immunosuppressive TME. Reactive oxygen species can be generated under light activation by the well-separated hole (h )-electron (e ) pairs owing to the heterojunction in BFO/BWO-PVP NPs. Interestingly, h can trigger the decomposition of H O to generate O for alleviating tumor hypoxia, which not only sensitizes photodynamic therapy (PDT) and radiotherapy (RT), but also promotes tumor-associated macrophages (TAMs) polarization from M2 to M1 phenotype, which is beneficial to decrease the expression of HIF-1α. Importantly, such a light-activated nanoplatform, combining with RT can efficiently activate and recruit cytotoxic T lymphocytes to infiltrate in tumor tissues, as well as stimulate TAMs to M1 phenotype, dramatically reverse the immunosuppressive TME into an immunoactive one, and further boost immune memory responses. Moreover, BFO/BWO-PVP NPs also present high performance for computed tomography imaging contrast. Taken together, this work offers a novel paradigm for achieving O self-supply of inorganic nanoagents and reshaping of the tumor immune microenvironment for effective inhibition of cancer as well as metastasis and recurrence.
免疫抑制性肿瘤微环境（TME）总是导致抗肿瘤免疫效果不佳，容易复发和转移。在此，构建了具有p-n型异质结的新型聚（乙烯基吡咯烷酮）（PVP）修饰的BiFeO₃/Bi₂WO₆（BFO/BWO）用于重塑免疫抑制性TME。由于BFO/BWO-PVP纳米颗粒中的异质结，光激活下可通过分离良好的空穴（h⁺）-电子（e⁻）对产生活性氧。有趣的是，h⁺可触发H₂O₂分解产生O₂以缓解肿瘤缺氧，这不仅使光动力疗法（PDT）和放射疗法（RT）敏感化，还促进肿瘤相关巨噬细胞（TAM）从M2表型向M1表型极化，有利于降低HIF-1α的表达。重要的是，这种光激活纳米平台与RT结合可有效激活并募集细胞毒性T淋巴细胞浸润肿瘤组织，以及刺激TAM向M1表型转变，显著将免疫抑制性TME逆转为免疫活性TME，并进一步增强免疫记忆反应。此外，BFO/BWO-PVP纳米颗粒在计算机断层扫描成像造影方面也表现出高性能。综上所述，这项工作为实现无机纳米剂的O₂自供应以及重塑肿瘤免疫微环境以有效抑制癌症以及转移和复发提供了一种新的范例。
