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利用甘露糖共轭二氢卟吩e6的抗肿瘤活性的光动力疗法可减少M2样肿瘤相关巨噬细胞。

Photodynamic therapy exploiting the anti-tumor activity of mannose-conjugated chlorin e6 reduced M2-like tumor-associated macrophages.

作者信息

Soyama Tatsuki, Sakuragi Akira, Oishi Daisuke, Kimura Yuka, Aoki Hiromasa, Nomoto Akihiro, Yano Shigenobu, Nishie Hirotada, Kataoka Hiromi, Aoyama Mineyoshi

机构信息

Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.

Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.

出版信息

Transl Oncol. 2021 Feb;14(2):101005. doi: 10.1016/j.tranon.2020.101005. Epub 2021 Jan 2.

DOI:10.1016/j.tranon.2020.101005
PMID:33401079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7785959/
Abstract

M2-like tumor-associated macrophages (M2-TAMs) in cancer tissues are intimately involved in cancer immunosuppression in addition to growth, invasion, angiogenesis, and metastasis. Hence, considerable attention has been focused on cancer immunotherapies targeting M2-TAMs. However, systemic therapies inhibit TAMs as well as other macrophages important for normal immune responses throughout the body. To stimulate tumor immunity with fewer side effects, we targeted M2-TAMs using photodynamic therapy (PDT), which damages cells via a nontoxic photosensitizer with harmless laser irradiation. We synthesized a light-sensitive compound, mannose-conjugated chlorin e6 (M-chlorin e6), which targets mannose receptors highly expressed on M2-TAMs. M-chlorin e6 accumulated more in tumor tissue than normal skin tissue of syngeneic model mice and was more rapidly excreted than the second-generation photosensitizer talaporfin sodium. Furthermore, M-chlorin e6 PDT significantly reduced the volume and weight of tumor tissue. Flow cytometric analysis revealed that M-chlorin e6 PDT decreased the proportion of M2-TAMs and increased that of anti-tumor macrophages, M1-like TAMs. M-chlorin e6 PDT also directly damaged and killed cancer cells in vitro. Our data indicate that M-chlorin e6 is a promising new therapeutic agent for cancer PDT.

摘要

癌症组织中的M2样肿瘤相关巨噬细胞（M2-TAM）除了参与癌症的生长、侵袭、血管生成和转移外，还密切参与癌症免疫抑制。因此，针对M2-TAM的癌症免疫疗法受到了广泛关注。然而，全身疗法在抑制TAM的同时，也会抑制对全身正常免疫反应很重要的其他巨噬细胞。为了在副作用较少的情况下刺激肿瘤免疫，我们使用光动力疗法（PDT）靶向M2-TAM，该疗法通过无毒的光敏剂和无害的激光照射来损伤细胞。我们合成了一种光敏化合物，甘露糖共轭二氢卟吩e6（M-二氢卟吩e6），它靶向在M2-TAM上高度表达的甘露糖受体。在同基因模型小鼠中，M-二氢卟吩e6在肿瘤组织中的积累比正常皮肤组织更多，并且比第二代光敏剂他拉泊芬钠排泄得更快。此外，M-二氢卟吩e6 PDT显著降低了肿瘤组织的体积和重量。流式细胞术分析显示，M-二氢卟吩e6 PDT降低了M2-TAM的比例，增加了抗肿瘤巨噬细胞M1样TAM的比例。M-二氢卟吩e6 PDT在体外也能直接损伤并杀死癌细胞。我们的数据表明，M-二氢卟吩e6是一种有前景的新型癌症PDT治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f4/7785959/b17998cacacc/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f4/7785959/bca31cb89d03/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f4/7785959/9fea9cfff76f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f4/7785959/2a516c4514ce/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f4/7785959/b17998cacacc/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f4/7785959/bca31cb89d03/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f4/7785959/9fea9cfff76f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f4/7785959/2a516c4514ce/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60f4/7785959/b17998cacacc/gr4.jpg

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