2. Academic Validation
  3. Maltotriose Conjugation to a Chlorin Derivative Enhances the Antitumor Effects of Photodynamic Therapy in Peritoneal Dissemination of Pancreatic Cancer

Maltotriose Conjugation to a Chlorin Derivative Enhances the Antitumor Effects of Photodynamic Therapy in Peritoneal Dissemination of Pancreatic Cancer

  • Mol Cancer Ther. 2017 Jun;16(6):1124-1132. doi: 10.1158/1535-7163.MCT-16-0670.
Akihisa Kato 1,  Hiromi Kataoka 2,  Shigenobu Yano 3,  Kazuki Hayashi 1,  Noriyuki Hayashi 1,  Mamoru Tanaka 1,  Itaru Naitoh 1,  Tesshin Ban 1,  Katsuyuki Miyabe 1,  Hiromu Kondo 1,  Michihiro Yoshida 1,  Yasuaki Fujita 1,  Yasuki Hori 1,  Makoto Natsume 1,  Takashi Murakami 4,  Atsushi Narumi 5,  Akihiro Nomoto 6,  Aya Naiki-Ito 7,  Satoru Takahashi 7,  Takashi Joh 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  • 2 Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. hkataoka@med.nagoya-cu.ac.jp.
  • 3 Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
  • 4 Laboratory of Tumor Biology, Takasaki University of Health and Welfare, Takasaki, Japan.
  • 5 Department of Organic Materials Science, Graduate School of Organic Materials Science, Yamagata University, Yonezawa, Japan.
  • 6 Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Osaka, Japan.
  • 7 Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
PMID: 28292934 DOI: 10.1158/1535-7163.MCT-16-0670
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 Mal3 molecules 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.

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