title: Maltotriose Conjugation to a Chlorin Derivative Enhances the Antitumor Effects of Photodynamic Therapy in Peritoneal Dissemination of Pancreatic Cancer.
abstract: Peritoneal dissemination is a major clinical issue associated with dismal prognosis and poor quality of life for patients with pancreatic cancer; however, no effective treatment strategies have been established. Herein, we evaluated the effects of photodynamic therapy (PDT) with maltotriose-conjugated chlorin (Mal3-chlorin) in culture and in a peritoneal disseminated mice model of pancreatic cancer. The Mal3-chlorin was prepared as a water-soluble chlorin derivative conjugated with four Mal3molecules to improve cancer selectivity.In vitro, Mal3-chlorin showed superior uptake into pancreatic cancer cells compared with talaporfin, which is clinically used. Moreover, the strong cytotoxic effects of PDT with Mal3-chlorin occurred via apoptosis and reactive oxygen species generation, whereas Mal3-chlorin alone did not cause any cytotoxicity in pancreatic cancer cells. Notably, using a peritoneal disseminated mice model, we demonstrated that Mal3-chlorin accumulated in xenograft tumors and suppressed both tumor growth and ascites formation with PDT. Furthermore, PDT with Mal3-chlorin induced robust apoptosis in peritoneal disseminated tumors, as indicated by immunohistochemistry. Taken together, these findings implicate Mal3-chlorin as a potential next-generation photosensitizer for PDT and the basis of a new strategy for managing peritoneal dissemination of pancreatic cancer.Mol Cancer Ther; 16(6); 1124-32. ©2017 AACR.
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kato
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. hkataoka@med.nagoya-cu.ac.jp.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kataoka
authors.affiliation: Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yano
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Naitoh
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Tesshin
authors.initials: T
authors.lastname: Ban
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miyabe
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Hori
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Natsume
authors.affiliation: Laboratory of Tumor Biology, Takasaki University of Health and Welfare, Takasaki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Organic Materials Science, Graduate School of Organic Materials Science, Yamagata University, Yonezawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Narumi
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nomoto
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Naiki-Ito
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Joh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000556:secondary* / Q000628:therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014312:Trisaccharides / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; D014312:Trisaccharides; C006969:chlorin; C008317:maltotriose; D020169:Caspases