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通过改造光敏剂受体优化活性氧生成促进巨噬细胞向M1表型重编程
作者:小柯机器人 发布时间:2020/11/27 14:44:19

南方科技大学生物医学工程系李凯研究小组近日取得一项新成果,他们发现可以通过改造光敏剂受体影响活性氧(ROS)生成,从而促进巨噬细胞向M1表型转化以增强抗肿瘤免疫活性。 这一研究成果发表在2020年11月25日的《德国应用化学》上。

在该研究中,课题组理性设计与合成了三种在产生ROS方面具有聚集增强效应、具有供体-受体结构的光敏剂。这些分子产生ROS的效率可以通过改变受体结构来调节,从而产生不同的激活巨噬细胞的能力。令人惊讶的是,课题组发现I型机制产生的细胞外ROS主要负责将巨噬细胞从促癌型(M2)重新编程为抗癌性(M1)。进一步体内实验证明,这种聚集增强效应的光敏剂只需一次光动力治疗即可触发光动力免疫疗法,有效抑制小鼠中的肿瘤生长,而在巨噬细胞敲除的小鼠中治疗效果明显消失。

综上所述,这一策略为设计能活化巨噬细胞的光敏剂分子提供了重要指导原则,并为巨噬细胞活化在光动力免疫疗法中的工作原理提供了新的见解。

据悉,通过光动力疗法(PDT)将肿瘤相关巨噬细胞重编程为抗肿瘤的M1表型,是一种克服肿瘤微环境的免疫抑制和促进抗肿瘤免疫治疗的有前途的策略。但产生活性氧的I型和II型机理与相应的巨噬细胞极化效率之间的关系尚不清楚。

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

期刊信息

Angewandte Chemie:《德国应用化学》,创刊于1887年。隶属于德国化学会,最新IF:12.959
官方网址:https://onlinelibrary.wiley.com/journal/15213773
投稿链接:https://www.editorialmanager.com/anie/default.aspx