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 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.