Acceptor Engineering for Optimized ROS Generation Facilitates Reprogramming Macrophages to M1 Phenotype in Photodynamic Immunotherapy
| Autor: | Jen-Shyang Ni, Kai Li, Yaxi Li, Menglei Zha, Yao Tu, Guang Yang |
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| Rok vydání: | 2021 |
| Předmět: |
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medicine.medical_treatment Macrophage polarization Antineoplastic Agents Photodynamic therapy 010402 general chemistry 01 natural sciences Catalysis Mice In vivo Cell Line Tumor Neoplasms medicine Animals Photosensitizer chemistry.chemical_classification Mice Inbred BALB C Tumor microenvironment Reactive oxygen species Aniline Compounds Photosensitizing Agents 010405 organic chemistry Chemistry Macrophages General Medicine General Chemistry Immunotherapy Cellular Reprogramming 0104 chemical sciences RAW 264.7 Cells Photochemotherapy Cancer research Female Reactive Oxygen Species Reprogramming |
| Zdroj: | Angewandte Chemie International Edition. 60:5386-5393 |
| ISSN: | 1521-3773 1433-7851 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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