Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, 518055, China.
Angew Chem Int Ed Engl. 2021 Mar 1;60(10):5386-5393. doi: 10.1002/anie.202013228. Epub 2021 Jan 19.
Reprogramming tumor-associated macrophages to an antitumor M1 phenotype by photodynamic therapy is a promising strategy to overcome the immunosuppression of tumor microenvironment for boosted immunotherapy. However, it remains unclear how the reactive oxygen species (ROS) generated from type I and II mechanisms, relate to the macrophage polarization efficacy. Herein, we design and synthesize three donor-acceptor structured photosensitizers with varied ROS-generating efficiencies. Surprisingly, we discovered that the extracellular ROS generated from type I mechanism are mainly responsible for reprogramming the macrophages from a pro-tumor type (M2) to an anti-tumor state (M1). In vivo experiments prove that the photosensitizer can trigger photodynamic immunotherapy for effective suppression of the tumor growth, while the therapeutic outcome is abolished with depleted macrophages. Overall, our strategy highlights the designing guideline of macrophage-activatable photosensitizers.
通过光动力疗法将肿瘤相关巨噬细胞重编程为抗肿瘤 M1 表型是克服肿瘤微环境免疫抑制以增强免疫治疗的一种有前途的策略。然而，目前尚不清楚来自 I 型和 II 型机制的活性氧 (ROS) 如何与巨噬细胞极化效果相关。在此，我们设计并合成了三种具有不同 ROS 生成效率的供体-受体结构的光动力试剂。令人惊讶的是，我们发现来自 I 型机制的细胞外 ROS 主要负责将巨噬细胞从促肿瘤类型 (M2) 重编程为抗肿瘤状态 (M1)。体内实验证明，该光敏剂可以引发光动力免疫治疗，有效抑制肿瘤生长，而耗尽巨噬细胞则会消除治疗效果。总的来说，我们的策略强调了巨噬细胞激活型光动力试剂的设计准则。
