Dual Tumor Microenvironment Remodeling by Glucose-Contained Radical Copolymer for MRI-Guided Photoimmunotherapy
Dual Tumor Microenvironment Remodeling by Glucose-Contained Radical Copolymer for MRI-Guided Photoimmunotherapy
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DOI：
10.1002/adma.202107674
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发表时间：
2021-11-17
影响因子：
29.4
通讯作者：
Li, Zibiao
中科院分区：
文献类型：
--
作者：
Cheng, Hongwei;Fan, Xiaoshan;Li, Zibiao
糖代谢异常和免疫逃避被认为是癌症的两个标志，这导致治疗效率低下和肿瘤进展。本文中，设计了由葡萄糖和PEO-b-PLLA嵌段共聚物（葡萄糖-PEO-b-PLLA-克里思）远端的克里思（2，2，6，6-四甲基哌啶-1-基）氧基）组成的新型材料系统，以包封临床治疗剂CUDC 101和光敏剂IR 780。由所设计的共聚物形成的特定核-壳杆结构使得克里思自由基对还原诱导的磁共振成像（MRI）沉默具有优异的稳定性。由葡萄糖赋予的肿瘤靶向部分为自由基共聚物提供了出色的多模态成像能力，包括MRI、光声成像和荧光成像。实现了CUDC 101和IR 780的有效递送，以通过IR 780介导的光动力疗法（PDT）和CUDC 101触发的CD 47抑制来协同抗肿瘤免疫激活，显示肿瘤相关巨噬细胞（TAM）的M1表型极化。更有趣的是，这项研究表明PDT刺激的p53也可以再教育TAM，提供了一种使用双重肿瘤微环境重塑的组合策略，以实现从冷免疫抑制到热免疫应答肿瘤微环境转变的协同效应。
Aberrant glucose metabolism and immune evasion are recognized as two hallmarks of cancer, which contribute to poor treatment efficiency and tumor progression. Herein, a novel material system consisting of a glucose and TEMPO (2,2,6,6-tetramethylpiperidin-1-yl)oxyl) at the distal ends of PEO-b-PLLA block copolymer (glucose-PEO-b-PLLA-TEMPO), is designed to encapsulate clinical therapeutics CUDC101 and photosensitizer IR780. The specific core-shell rod structure formed by the designed copolymer renders TEMPO radicals excellent stability against reduction-induced magnetic resonance imaging (MRI) silence. Tumor-targeting moiety endowed by glucose provides the radical copolymer outstanding multimodal imaging capabilities, including MRI, photoacoustic imaging, and fluorescence imaging. Efficient delivery of CUDC101 and IR780 is achieved to synergize the antitumor immune activation through IR780-mediated photodynamic therapy (PDT) and CUDC101-triggered CD47 inhibition, showing M1 phenotype polarization of tumor-associated macrophages (TAMs). More intriguingly, this study demonstrates PDT-stimulated p53 can also re-educate TAMs, providing a combined strategy of using dual tumor microenvironment remodeling to achieve the synergistic effect in the transition from cold immunosuppressive to hot immunoresponsive tumor microenvironment.