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

Tomohiro Osaki,Yoshiharu Okamoto,Inoru Yokoe,Shota Hibino,Mamoru Tanaka,Yuji Mikata,Hiromi Kataoka,Shigenobu Yano,Akihiro Nomoto,Hiroaki Yamaguchi

doi:10.3390/cancers11050636

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.

Highlights

Breast cancer is currently the most commonly diagnosed cancer and one of the deadliest diseases in women [1]
We evaluated the cytotoxicity of photodynamic therapy (PDT) with glucose-conjugated chlorin e6 (G-Ce6) compared to NPe6, a hydrophilic chlorin agent derived from chlorophyll
PDT using G-Ce6 was effective for canine mammary carcinoma (CMC) and G-Ce6 was rapidly cleared from the plasma. These results suggested that CMCs are useful for preclinical research in comparative oncology and would be an optimal design for human clinical trials

Summary

Introduction

Breast cancer is currently the most commonly diagnosed cancer and one of the deadliest diseases in women [1]. PDT, a minimally invasive cancer treatment, relies on the combination of a photosensitizer, light, and oxygen to eliminate tumor cells or microorganisms. These are nontoxic individually, when combined, they initiate a photochemical reaction that culminates in the generation of a highly reactive species termed singlet oxygen (1 O2 ) or radicals [2,3]. These reactive species can rapidly cause substantial toxicity, subsequently leading to cell death via apoptosis, necrosis, or autophagy [2,3]

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