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Cancers (Basel). 2019 May 8;11(5). pii: E636. doi: 10.3390/cancers11050636.

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

Author information

1
Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. tosaki@muses.tottori-u.ac.jp.
2
Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. mayrupi@yahoo.co.jp.
3
Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. inoru.y@gmail.com.
4
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. hiroaki_yamaguchi@sanbo-chem.co.jp.
5
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. nomoto@chem.osakafu-u.ac.jp.
6
KYOUSEI Science Center for Life and Nature, Nara Women's University, Kitauoyahigashi-machi, Nara 630-8506, Japan. yano-s@cc.nara-wu.ac.jp.
7
KYOUSEI Science Center for Life and Nature, Nara Women's University, Kitauoyahigashi-machi, Nara 630-8506, Japan. mikata@cc.nara-wu.ac.jp.
8
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. mtanaka77@gmail.com.
9
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. hkataoka@med.nagoya-cu.ac.jp.
10
Joint Department of Veterinary Clinical Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan. yokamoto@muses.tottori-u.ac.jp.

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.

KEYWORDS:

canine mammary carcinoma; glucose-conjugated chlorin e6; photodynamic therapy

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