Engineering a photosensitizer nanoplatform for amplified photodynamic immunotherapy via tumor microenvironment modulation,Nanoscale Horizons

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Engineering a photosensitizer nanoplatform for amplified photodynamic immunotherapy via tumor microenvironment modulation
Nanoscale Horizons ( IF 8.0 ) Pub Date : 2020-10-31 , DOI: 10.1039/d0nh00480d
Yaxin Zhou ₁ , Xiaomeng Ren , Zhaosheng Hou , Ningning Wang , Yue Jiang , Yuxia Luan

Affiliation

Photosensitizer-based photodynamic therapy (PDT) can not only kill tumor cells by the generated cytotoxic reactive oxygen species (ROS), but also trigger immunogenic cell death (ICD) and activate an immune response for immunotherapy. However, such photodynamic immunotherapy suffers from major obstacles in the tumor microenvironment. The hypoxic microenvironment greatly weakens PDT, while the immunosuppressive tumor microenvironment caused by aberrant tumor blood vessels and indoleamine 2,3-dioxygenase (IDO) leads to a significant reduction in immunotherapy. To overcome these obstacles, herein, an engineered photosensitizer nanoplatform is designed for amplified photodynamic immunotherapy by integrating chlorin e6 (Ce6, a photosensitizer), axitinib (AXT, a tyrosine kinase inhibitor) and dextro-1-methyl tryptophan (1MT, an IDO inhibitor). In our nanoplatform, AXT improves the tumor microenvironment by normalizing tumor blood vessels, which not only promotes PDT by reducing the level of hypoxia of the tumor microenvironment, but also promotes immunotherapy through facilitating infiltration of immune effector cells into the tumor and reversing the immunosuppressive effect of vascular endothelial growth factor (VEGF). Moreover, 1MT effectively inhibits the activity of IDO, further reducing the immunosuppressive nature of the tumor microenvironment. Therefore, this nanoplatform demonstrates an amplified photodynamic immunotherapy via tumor microenvironment modulation, exhibiting outstanding therapeutic efficacy against tumor growth and metastasis with negligible side toxicity. The current concept of engineering photosensitizer nanoplatforms for overcoming photodynamic immunotherapy obstacles provides a promising strategy against tumors.

中文翻译：

设计光敏剂纳米平台，通过肿瘤微环境调节放大光动力免疫治疗

基于光敏剂的光动力疗法（PDT）不仅可以通过产生的细胞毒性活性氧（ROS）杀死肿瘤细胞，还可以触发免疫原性细胞死亡（ICD）并激活免疫反应以进行免疫治疗。然而，这种光动力免疫疗法在肿瘤微环境中遇到了重大障碍。缺氧微环境大大削弱PDT，而异常肿瘤血管和吲哚胺2,3-双加氧酶（IDO）引起的免疫抑制肿瘤微环境导致免疫治疗显着降低。为了克服这些障碍，本文设计了一种工程光敏剂纳米平台，通过整合二氢卟酚 e6（Ce6，一种光敏剂）、阿西替尼（AXT，一种酪氨酸激酶抑制剂）和右旋 1-甲基色氨酸（1MT，一种 IDO 抑制剂），用于放大光动力免疫治疗。）。在我们的纳米平台中，AXT通过使肿瘤血管正常化来改善肿瘤微环境，不仅通过降低肿瘤微环境的缺氧水平来促进PDT，而且还通过促进免疫效应细胞浸润到肿瘤中并逆转免疫抑制作用来促进免疫治疗血管内皮生长因子（VEGF）。此外，1MT有效抑制IDO的活性，进一步降低肿瘤微环境的免疫抑制性质。因此，该纳米平台通过肿瘤微环境调节展示了放大的光动力免疫疗法，对肿瘤生长和转移表现出出色的治疗功效，且副作用可忽略不计。当前用于克服光动力免疫治疗障碍的工程光敏剂纳米平台的概念提供了一种有前途的抗肿瘤策略。

更新日期：2020-11-27

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