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Journal of Nanomaterials
Volume 2016, Article ID 4075803, 12 pages
http://dx.doi.org/10.1155/2016/4075803
Research Article

Redox-Responsive Nanophotosensitizer Composed of Chlorin e6-Conjugated Dextran for Photodynamic Treatment of Colon Cancer Cells

1Department of Surgery, Pusan National University Yangsan Hospital, Gyeongnam 626-770, Republic of Korea
2Biomedical Research Institute, Pusan National University Hospital, Pusan 602-739, Republic of Korea
3Department of Internal Medicine, Pusan National University Yangsan Hospital, Gyeongnam 626-770, Republic of Korea
4Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Gyeongnam 626-770, Republic of Korea

Received 6 September 2015; Revised 26 October 2015; Accepted 27 October 2015

Academic Editor: David Cornu

Copyright © 2016 Chong Woo Chu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We synthesized dextran-chlorin e6 conjugates having disulfide linkage for specific targeting of colonic region and cancer cells. Reductive end group of dextran was treated with sodium borocyanohydride and conjugated with cystamine. Cystamine end group was conjugated with carboxylic acid of chlorin e6 (DEX6ss). DEX6ss conjugates were formed as spherical nanoparticles with small sizes less than 100 nm. Chlorin e6 (Ce6) was specifically released from DEX6ss nanoparticles in the presence of dextranase or glutathione (GSH), indicating that DEX6ss nanoparticles have responsiveness against dextranase and redox-environment. In dark-toxicity test using normal cells and cancer cells, Ce6 and DEX6ss nanoparticles were practically nontoxic. Intracellular delivery of DEX6ss nanoparticles was significantly improved compared to Ce6 itself. DEX6ss nanoparticles achieved significantly higher ROS production and phototoxicity against HCT116 colon cancer cells than Ce6 itself. Furthermore, DEX6ss nanoparticles showed enhanced tumor targeting efficiency and longer retention in the tumor tissues at in vivo animal study with HCT116 tumor-bearing mice. Furthermore, DEX6ss nanoparticles have responsiveness against colonic enzyme, dextranase, indicating that they have potential of colon-specific delivery and dextranase-specific drug delivery capacity. We fabricated colon-specific and tumor-targetable nanophotosensitizer using DEX6ss conjugates. They showed improved cellular uptake ratio, phototoxicity, and colon-specificity. We suggest that DEX6ss nanoparticles can be considered as a promising candidate for PDT of colon cancer.