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Photodynamic therapy with glycoconjugated chlorin photosensitizer

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

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Eiko Otake

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

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Kan Torii

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

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Motoki Nakamura

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

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Akira Maeda

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

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Ryoto Tujii

Research Institute for Natural Sciences, Okayama University, Japan

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Haruo Akashi

Research Institute for Natural Sciences, Okayama University, Japan

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Hiromi Ohi

Endowed Research Section, Photomedical Science, Office of Society-Academia Collaboration for Innovation Kyoto University, Kyoto, Japan

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Shigenobu Yano

Endowed Research Section, Photomedical Science, Office of Society-Academia Collaboration for Innovation Kyoto University, Kyoto, Japan

Graduate School of Material Science, Nara Institute of Science and Technology, Nara, Japan

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Akimichi Morita

Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

Corresponding author, tel: +81 52-853-8261, fax: +81 52-852-5449.

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https://doi.org/10.1142/S1088424613500065Cited by:14 (Source: Crossref)

Abstract

Photodynamic therapy (PDT) effectively induces tumor cell apoptosis, but the tumor selectivity and photosensitivity of common photosensitizers, such as aspartyl chlorin (NPe6), are not sufficient. Cancer cells phagocytose glucose 3 to 20 times more efficiently than normal cells; therefore, we examined whether glycoconjugation improves photosensitizer tumor-localizability. HaCaT cells were incubated with H₂TFPC (unconjugated chlorin), H₂TFPC-SGlc (glycoconjugated chlorin), or NPe6, followed by irradiation with 633 nm LED light (16 J.cm^-2). PDT with 1 μM H₂TFPC-SGlc for 24 h induced significantly more apoptosis (annexinV⁺ cells: 74.5%) than PDT with either H₂TFPC (2.9%) or NPe6 (0.3%). Based on the IC₅₀, PDT with H₂TFPC-SGlc induced tumor cell death more efficiently than NPe6 or H₂TFPC in all cell lines examined. The addition of sodium azide, a singlet oxygen quencher, during irradiation significantly suppressed PDT-induced apoptosis in COLO679 cells (-0.4 ± 0.3% → 119 ± 44%), whereas coincubation with deuterium oxide, a singlet oxygen enhancer, enhanced PDT (72 ± 19 → 27 ± 5%). Confocal microscopy revealed that H₂TFPC-SGlc accumulated in lysosomes and Golgi bodies, but not in mitochondria or endoplasmic reticulum. In melanoma-bearing mice, intratumoral injection of H₂TFPC-SGlc (10^-8 mol or 10^-9 mol), followed 4 h later by irradiation with 633 nm LED light (150 J.cm^-2) controlled tumor growth for 13 consecutive days (10^-8 mol). Thus, PDT with H₂TFPC-SGlc effectively induces apoptosis in tumor cells via singlet oxygen induction.

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