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Macrophages mediated delivery of chlorin e6 and treatment of lung cancer by photodynamic reprogramming
International Immunopharmacology ( IF 4.8 ) Pub Date : 2021-09-22 , DOI: 10.1016/j.intimp.2021.108164
Ting-Ting Yu 1 , Xue-Yu Sang 1 , Ning Han 2 , Xing-Chun Peng 2 , Qi-Rui Li 2 , Xiang Xu 2 , Rong-Cheng Xiao 2 , Hua-Zhen Xu 3 , Xiao Chen 3 , Mei-Fang Wang 4 , Tong-Fei Li 1
Affiliation  

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.



中文翻译:

巨噬细胞介导二氢卟酚e6的传递和光动力重编程治疗肺癌

光动力疗法(PDT)是一种新兴的抗肿瘤策略。 光敏剂二氢卟酚e6(Ce6)可诱导光动力效应选择性地损伤肺癌细胞。 为了进一步提高其肿瘤靶向能力,巨噬细胞可作为载体将Ce6递送至肺癌。 肿瘤相关巨噬细胞(TAM)是肺癌免疫微环境中重要的免疫细胞。由于 TAM 的免疫抑制特性,TAM 在肿瘤促进中起着至关重要的作用,因此 TAM 的重编程表型已成为一种有前途的策略。 基于此,在本研究中,我们假设TAM可以作为载体将Ce6传递给肺癌,并通过光动力作用重编程为M1表型,从而介导抗肺癌疗效。 结果表明TAM可以负载Ce6并在没有近红外辐射(NIR)的情况下保持活力。 此外,它的活力在近红外后 10 小时内几乎没有下降。 负载 Ce6 的 TAM 可以将 Ce6 递送至肺癌细胞,并在 TAM 本身中保留一些药物。 NIR后,巨噬细胞的吞噬作用增强。GBP5、iNOS和MHC-II的表达上调,表明TAM极化为M1表型。 最后,研究还发现重编程的巨噬细胞可以抑制肺癌细胞的增殖,促进其凋亡。 这些结果表明,巨噬细胞可以将 Ce6 传递给肺癌,并通过光动力重编程表现出抗肺癌作用。 该研究提供了一种将光动力作用与抗肿瘤免疫疗法相结合的新方法。

更新日期:2021-09-23
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