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Open AccessArticle

Novel Photosensitizer β-Mannose-Conjugated Chlorin e6 as a Potent Anticancer Agent for Human Glioblastoma U251 Cells

1
Department of Environmental Health, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, 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
Department of Neurosurgery, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku, Tokyo 160-0023, Japan
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Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan
5
Department of Organic Materials Science, Graduate School of Organic Materials Science, Yamagata University, Jonan 4-3-16, Yonezawa 992-8510, Japan
6
KYOUSEI Science Center for Life and Nature, Nara Women’s University, Kitauoya-Higashimachi, Nara 630-8506, Japan
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(10), 316; https://doi.org/10.3390/ph13100316
Received: 1 October 2020 / Revised: 13 October 2020 / Accepted: 13 October 2020 / Published: 16 October 2020
(This article belongs to the Special Issue Photodynamic Therapy 2021)
A photosensitizer is a molecular drug for photodynamic diagnosis and photodynamic therapy (PDT) against cancer. Many studies have developed photosensitizers, but improvements in their cost, efficacy, and side effects are needed for better PDT of patients. In the present study, we developed a novel photosensitizer β-mannose-conjugated chlorin e6 (β-M-Ce6) and investigated its PDT effects in human glioblastoma U251 cells. U251 cells were incubated with β-M-Ce6, followed by laser irradiation. Cell viability was determined using the Cell Counting Kit-8 assay. The PDT effects of β-M-Ce6 were compared with those of talaporfin sodium (TS) and our previously reported photosensitizer β-glucose-conjugated chlorin e6 (β-G-Ce6). Cellular uptake of each photosensitizer and subcellular distribution were analyzed by fluorescence microscopy. β-M-Ce6 showed 1000× more potent PDT effects than those of TS, and these were similar to those of β-G-Ce6. β-M-Ce6 accumulation in U251 cells was much faster than TS accumulation and distributed to several organelles such as the Golgi apparatus, mitochondria, and lysosomes. This rapid cellular uptake was inhibited by low temperature, which suggested that β-M-Ce6 uptake uses biological machinery. β-M-Ce6 showed potent PDT anti-cancer effects compared with clinically approved TS, which is a possible candidate as a next generation photosensitizer in cancer therapy. View Full-Text
Keywords: β-mannose-conjugated chlorin e6; talaporfin sodium; glioblastoma; U251; photodynamic therapy; PDT β-mannose-conjugated chlorin e6; talaporfin sodium; glioblastoma; U251; photodynamic therapy; PDT
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Shinoda, Y.; Kujirai, K.; Aoki, K.; Morita, M.; Masuda, M.; Zhang, L.; Kaixin, Z.; Nomoto, A.; Takahashi, T.; Tsuneoka, Y.; Akimoto, J.; Kataoka, H.; Rachi, R.; Narumi, A.; Yoshimura, T.; Yano, S.; Fujiwara, Y. Novel Photosensitizer β-Mannose-Conjugated Chlorin e6 as a Potent Anticancer Agent for Human Glioblastoma U251 Cells. Pharmaceuticals 2020, 13, 316.

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