Macrophages mediated delivery of chlorin e6 and treatment of lung cancer by photodynamic reprogramming

• Published in: International immunopharmacology 2021-11, Vol.100, p.108164-108164, Article 108164
• Main Authors: Yu, Ting-Ting, Sang, Xue-Yu, Han, Ning, Peng, Xing-Chun, Li, Qi-Rui, Xu, Xiang, Xiao, Rong-Cheng, Xu, Hua-Zhen, Chen, Xiao, Wang, Mei-Fang, Li, Tong-Fei
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Carcinoma, Lewis Lung - drug therapy; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - metabolism; Carcinoma, Lewis Lung - pathology; Cell Line, Tumor; Cell Proliferation; Chlorin e6; Chlorophyllides - metabolism; Chlorophyllides - pharmacology; Coculture Techniques; Genotype & phenotype; I.R. radiation; Immunosuppressive agents; Immunotherapy; Irradiation; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Macrophages; Macrophages reprogramming; Major histocompatibility complex; Mice; Microenvironments; Near infrared radiation; Nitric-oxide synthase; Phagocytosis; Phenotype; Phenotypes; Photochemotherapy; Photodynamic effect; Photodynamic therapy; Radiation-Sensitizing Agents - metabolism; Radiation-Sensitizing Agents - pharmacology; RAW 264.7 Cells; Tumor Microenvironment; Tumor-Associated Macrophages - immunology; Tumor-Associated Macrophages - metabolism; Tumorigenesis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.108164

•Photodynamic action under certain conditions could remodel phenotype of macrophages.•The reprogrammed macrophages triggers anti-lung cancer effects.•The present study provides a novel strategy to perform anti-tumor immunotherapy. Photodynamic therapy (PDT) is an emerging anti-tumor strategy.Photosensitizer chlorin e6 (Ce6) can induce photodynamic effect to selectively damage lung cancer cells.In order to further improve its tumor targeting ability, macrophages can be applied as carrier to deliver Ce6 to lung cancer.Tumor associated macrophages (TAM) are important immunocytes in lung cancer immune microenvironment. TAM play crucial role in tumor promotion due to the Immunosuppressive property, reprogramming phenotype of TAM therefore has become a promising strategy.Based on this, in the present study, we suppose that TAM can be used as carrier to deliver Ce6 to lung cancer and be reprogrammed to M1 phenotype by photodynamic action to mediate anti-lung cancer efficacy.The results showed TAM could load with Ce6 and keep viability in the absence of near infrared irradiation (NIR).Moreover, Its viability decreased little within 10 h after NIR.Ce6-loaded TAM could deliver Ce6 to lung cancer cells and retain some drugs in TAM per se.After NIR, phagocytosis of macrophages was enhanced. The expressions of GBP5, iNOS and MHC-II was up-regulated, which indicated TAM were polarized to M1 phenotype.Finally, the study also found the reprogrammed macrophages could inhibit the proliferation and promote the apoptosis of lung cancer cells.These results suggested that macrophages could deliver Ce6 to lung cancer and exhibit anti-lung cancer effect through photodynamic reprogramming.This study provides a novel approach for combining photodynamic action with anti-tumor immunotherapy.