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

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

doi:10.1016/j.tranon.2020.101005

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

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

Authors

Affiliations

¹ Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
² Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
³ KYOUSEI Science Center for Life and Nature, Nara Women's University, Kitauoya-Higashimachi, Nara 630-8506, Japan.
⁴ Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Nagoya 467-8601, Japan.
⁵ Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. Electronic address: aomine@phar.nagoya-cu.ac.jp.

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.

Keywords: Mannose-conjugated chlorin e6; Photodynamic therapy; Tumor immunity; Tumor microenvironment; Tumor-associated macrophage.