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
  • 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. [email protected].
  • 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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