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A Basic Study of Photodynamic Therapy with Glucose-Conjugated Chlorin e6 Using Mammary Carcinoma Xenografts

1
Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, 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, Kitauoyahigashi-machi, Nara 630-8506, Japan
4
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 636; https://doi.org/10.3390/cancers11050636
Received: 7 March 2019 / Revised: 2 May 2019 / Accepted: 6 May 2019 / Published: 8 May 2019
(This article belongs to the Special Issue Photodynamic Therapy (PDT) in Oncology)
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Abstract

By using the Warburg effect—a phenomenon where tumors consume higher glucose levels than normal cells—on cancer cells to enhance the effect of photodynamic therapy (PDT), we developed a new photosensitizer, glucose-conjugated chlorin e6 (G-Ce6). We analyzed the efficacy of PDT with G-Ce6 against canine mammary carcinoma (CMC) in vitro and in vivo. The pharmacokinetics of G-Ce6 at 2, 5, and 20 mg/kg was examined in normal dogs, whereas its intracellular localization, concentration, and photodynamic effects were investigated in vitro using CMC cells (SNP cells). G-Ce6 (10 mg/kg) was administered in vivo at 5 min or 3 h before laser irradiation to SNP tumor-bearing murine models. The in vitro study revealed that G-Ce6 was mainly localized to the lysosomes. Cell viability decreased in a G-Ce6 concentration- and light intensity-dependent manner in the PDT group. Cell death induced by PDT with G-Ce6 was not inhibited by an apoptosis inhibitor. In the in vivo study, 5-min-interval PDT exhibited greater effects than 3-h-interval PDT. The mean maximum blood concentration and half-life of G-Ce6 (2 mg/kg) were 15.19 ± 4.44 μg/mL and 3.02 ± 0.58 h, respectively. Thus, 5-min-interval PDT with G-Ce6 was considered effective against CMC. View Full-Text
Keywords: photodynamic therapy; glucose-conjugated chlorin e6; canine mammary carcinoma photodynamic therapy; glucose-conjugated chlorin e6; canine mammary carcinoma
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Osaki, T.; Hibino, S.; Yokoe, I.; Yamaguchi, H.; Nomoto, A.; Yano, S.; Mikata, Y.; Tanaka, M.; Kataoka, H.; Okamoto, Y. A Basic Study of Photodynamic Therapy with Glucose-Conjugated Chlorin e6 Using Mammary Carcinoma Xenografts. Cancers 2019, 11, 636.

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