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
Department of respiratory, Taihe Hospital of Shiyan, Hubei University of Medicine, Renmin road No. 30, Shiyan, Hubei 442000, China; Department of Pharmacology, School of Basic Medical Sciences, Hubei University of Medicine, Renmin road No. 30, Shiyan, Hubei 442000, China; Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Renmin road No. 30, Shiyan, Hubei 442000, China.
Department of Pharmacology, School of Basic Medical Sciences, Hubei University of Medicine, Renmin road No. 30, Shiyan, Hubei 442000, China; Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Renmin road No. 30, Shiyan, Hubei 442000, China.
Int Immunopharmacol. 2021 Nov;100:108164. doi: 10.1016/j.intimp.2021.108164. Epub 2021 Sep 22.
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.
光动力疗法(PDT)是一种新兴的抗肿瘤策略。光敏剂二氢卟吩e6(Ce6)可诱导光动力效应以选择性损伤肺癌细胞。为了进一步提高其肿瘤靶向能力,可将巨噬细胞用作载体将Ce6递送至肺癌。肿瘤相关巨噬细胞(TAM)是肺癌免疫微环境中的重要免疫细胞。由于其免疫抑制特性,TAM在肿瘤进展中起关键作用,因此重编程TAM的表型已成为一种有前景的策略。基于此,在本研究中,我们推测TAM可作为载体将Ce6递送至肺癌,并通过光动力作用重编程为M1表型以介导抗肺癌疗效。结果显示TAM可负载Ce6并在无近红外辐射(NIR)的情况下保持活力。此外,在NIR照射后10小时内其活力下降很少。负载Ce6的TAM可将Ce6递送至肺癌细胞,并在TAM本身中保留一些药物。NIR照射后,巨噬细胞的吞噬作用增强。GBP5、iNOS和MHC-II的表达上调,这表明TAM已极化为M1表型。最后,该研究还发现重编程的巨噬细胞可抑制肺癌细胞的增殖并促进其凋亡。这些结果表明巨噬细胞可将Ce6递送至肺癌,并通过光动力重编程发挥抗肺癌作用。本研究为光动力作用与抗肿瘤免疫疗法的联合提供了一种新方法。