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15357163mct140348-sup-130482_1_supp_2666894_nc4kw2.pptx (557.07 kB)

Supplementary Figure S7 from A Novel Photodynamic Therapy Targeting Cancer Cells and Tumor-Associated Macrophages

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posted on 2023-04-03, 14:21 authored by Noriyuki Hayashi, Hiromi Kataoka, Shigenobu Yano, Mamoru Tanaka, Kazuhiro Moriwaki, Haruo Akashi, Shugo Suzuki, Yoshinori Mori, Eiji Kubota, Satoshi Tanida, Satoru Takahashi, Takashi Joh

Excess mannose reduced binding of M-chlorin to the macrophages and tumor cells in a dose-dependent manner.

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ARTICLE ABSTRACT

Tumor-associated macrophages (TAM) in cancer stroma play important roles for cancer cell growth, invasion, angiogenesis, and metastases. We synthesized a novel photosensitizer, mannose-conjugated chlorin (M-chlorin), designed to bind mannose receptors highly expressed on TAMs. We evaluated the newly available photodynamic therapy (PDT) with M-chlorin against gastric and colon cancer. We evaluated PDT with M-chlorin for in vitro cytotoxicity and apoptosis induction in cancer cells compared with chlorin alone and glucose-conjugated chlorin (G-chlorin). The subcellular localization of M-chlorin was observed by confocal microscopy, and the M-chlorin PDT effects against TAMs including THP-1–induced M2-polarized macrophages were evaluated. Anticancer effects were also investigated in an allograft model where cytotoxic effects against TAMs in the cancer cell stroma were analyzed by immunohistochemistry. M-chlorin PDT strongly induced cell death in cancer cells to almost the same extent as G-chlorin PDT by inducing apoptosis. M-chlorin was incorporated into cancer cells where it localized mainly in lysosomes and endoplasmic reticula. M-chlorin PDT revealed strong cytotoxicity for M2 macrophages induced from THP-1 cell lines, and it induced stronger cytotoxicity than G-chlorin PDT in the allograft model through killing both cancer cells and TAMs in the cancer stroma. The M-chlorin PDT produced strong cytotoxicity against cancer tissue by inducing apoptosis of both cancer cells and TAMs in the cancer stroma. This novel PDT thus stands as a new candidate for very effective, next-generation PDT. Mol Cancer Ther; 14(2); 452–60. ©2014 AACR.

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