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- Title
Redox-Responsive Nanophotosensitizer Composed of Chlorin e6-Conjugated Dextran for Photodynamic Treatment of Colon Cancer Cells.
- Authors
Chu, Chong Woo; Ryu, Je Ho; Jeong, Young-IL; Kwak, Tae Won; Lee, Hye Lim; Kim, Hyun Yul; Son, Gyung Mo; Kim, Hyung Wook; Kang, Dae Hwan
- 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.
- Subjects
COLON cancer treatment; PHOTODYNAMIC therapy; PHOTOSENSITIZERS; OXIDATION-reduction reaction; DEXTRAN; BIOCONJUGATES; CANCER cells
- Publication
Journal of Nanomaterials, 2016, p1
- ISSN
1687-4110
- Publication type
Article
- DOI
10.1155/2016/4075803