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  • Title: Excellent antitumor effects for gastrointestinal cancers using photodynamic therapy with a novel glucose conjugated chlorin e6.
    Author: Nishie H, Kataoka H, Yano S, Yamaguchi H, Nomoto A, Tanaka M, Kato A, Shimura T, Mizoshita T, Kubota E, Tanida S, Joh T.
    Journal: Biochem Biophys Res Commun; 2018 Feb 19; 496(4):1204-1209. PubMed ID: 29408755.
    Abstract:
    BACKGROUND: Photodynamic therapy (PDT) exploits the reaction between photosensitizer and irradiated light to generate potentially therapeutic reactive oxygen species such as singlet oxygen in cancer cells. We have reported several sugar-conjugated chlorins that express stronger antitumor effects in PDT than talaporfin sodium (TS), a second-generation photosensitizer clinically used in Japan. In this study, we developed a novel glucose-conjugated chlorin e6 (G-chlorin e6) and evaluated its antitumor effects. METHODS: G-chlorin e6 was synthesized with a core photosensitizer chlorin e6 conjugated to glucose. We measured the half maximal inhibitory concentration (IC50) to compare the PDT effects of G-chlorin e6 and TS, and flow cytometry was performed to examine the accumulation of G-chlorin e6 in cancer cells. We also compared the accumulation of G-chlorin e6 between normal immortalized esophageal epithelial cells and esophageal cancer cells. Antitumor effects of G-chlorin e6 PDT were finally analyzed in allograft tumor mouse models. RESULTS: PDT in vitro using G-chlorin e6 elicited 9, 000-34,000 times stronger antitumor effects than TS, and there was 70-190 times more G-chlorin e6 accumulated than TS by flow cytometry. G-chlorin e6 accumulated more selectively in esophageal cancer cells than in esophageal immortalized epithelial cells, and in an allograft model, PDT with G-chlorin e6 showed very strong antitumor effects and a 40% complete response (CR) rate. CONCLUSIONS: G-chlorin e6 showed excellent tumor selectivity, and PDT using G-chlorin e6 revealed the strongest anti-tumor effects among all sugar-conjugated chlorins that we have studied. G-chlorin e6 is considered to be the best photosensitizer for next-generation PDT.
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