通過改造光敏劑受體優化活性氧生成促進巨噬細胞向M1表型重編程
作者：
小柯機器人發布時間：2020/11/27 14:44:19
南方科技大學生物醫學工程系李凱研究小組近日取得一項新成果，他們發現可以通過改造光敏劑受體影響活性氧（ROS）生成，從而促進巨噬細胞向M1表型轉化以增強抗腫瘤免疫活性。 這一研究成果發表在2020年11月25日的《德國應用化學》上。
在該研究中，課題組理性設計與合成了三種在產生ROS方面具有聚集增強效應、具有供體-受體結構的光敏劑。這些分子產生ROS的效率可以通過改變受體結構來調節，從而產生不同的激活巨噬細胞的能力。令人驚訝的是，課題組發現I型機制產生的細胞外ROS主要負責將巨噬細胞從促癌型（M2）重新編程為抗癌性（M1）。進一步體內實驗證明，這種聚集增強效應的光敏劑只需一次光動力治療即可觸發光動力免疫療法，有效抑制小鼠中的腫瘤生長，而在巨噬細胞敲除的小鼠中治療效果明顯消失。
綜上所述，這一策略為設計能活化巨噬細胞的光敏劑分子提供了重要指導原則，並為巨噬細胞活化在光動力免疫療法中的工作原理提供了新的見解。
據悉，通過光動力療法（PDT）將腫瘤相關巨噬細胞重編程為抗腫瘤的M1表型，是一種克服腫瘤微環境的免疫抑制和促進抗腫瘤免疫治療的有前途的策略。但產生活性氧的I型和II型機理與相應的巨噬細胞極化效率之間的關係尚不清楚。
附：英文原文
Title: Acceptor Engineering for Optimized ROS Generation Facilitates Reprogramming Macrophages to M1 Phenotype in Photodynamic Immunotherapy
Author: Guang Yang, Jen-Shyang Ni, Yaxi Li, Menglei Zha, Yao Tu, Kai Li
Issue&Volume: 25 November 2020
Abstract: Reprogramming tumor‐associated macrophages to an antitumor M1 phenotype by photodynamic therapy (PDT) is a promising strategy to overcome the immunosuppression of tumor microenvironment for boosted cancer immunotherapy. However, it still remains unclear how the reactive oxygen species (ROS) generated from type I and II mechanisms relate to the corresponding macrophage polarization efficacy. In this contribution, we rationally design and synthesize three donor‐acceptor structured photosensitizers with aggregation‐enhanced ROS generation. Their ROS‐generating efficiencies can be adjusted by changing the acceptor, resulting in varied capabilities to activate macrophages. Surprisingly, we discover 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 further prove that the AIEgen photosensitizer can trigger photodynamic immunotherapy for effective suppression of the tumor growth in mice with a single PDT treatment, while the therapeutic outcome is significantly abolished in the mice with depleted macrophages. Overall, our strategy highlights the molecular designing guideline of macrophage‐activatable photosensitizers and provides new insights into the working principle of macrophage activation in photodynamic immunotherapy.
DOI: 10.1002/anie.202013228
Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202013228