Journal
MOLECULAR CANCER THERAPEUTICS
Volume 16, Issue 6, Pages 1124-1132Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-16-0670
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Funding
- JSPS KAKENHI [26460947, 19350031, 25288028]
- Translational Research Network Program of the Japan Agency for Medical Research and Development, AMED
- Japan-German Exchange Program
- JSPS
- Deutsche Forschungsgemeinschaft (DFG)
- Pancreas Research Foundation of Japan
- Grants-in-Aid for Scientific Research [25288028, 19350031, 26460947] Funding Source: KAKEN
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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 Mal(3)-chlorin alone did not cause any cytotoxicity in pancreatic cancer cells. Notably, using a peritoneal disseminated mice model, we demonstrated that Mal(3)-chlorin accumulated in xenograft tumors and suppressed both tumor growth and ascites formation with PDT. Furthermore, PDT with Mal(3)-chlorin induced robust apoptosis in peritoneal disseminated tumors, as indicated by immunohistochemistry. Taken together, these findings implicate Mal(3)-chlorin as a potential next-generation photosensitizer for PDT and the basis of a new strategy for managing peritoneal dissemination of pancreatic cancer. (C)2017 AACR.
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