title: Conjugation of the photosensitizer Chlorin e6 to pluronic F127 for enhanced cellular internalization for photodynamic therapy.
abstract: To improve the cellular internalization and tumor-specific targeting efficiency of a photosensitizer, Chlorin e6 (Ce6), was conjugated to Pluronic F127(®) (PF127) by esterification between the carboxylic groups of Ce6 and the two hydroxyl groups of PF127 (PCe6). After conjugation, two different PCe6 conjugates, PF127/Ce6 (PCe6-1) and Ce6/PF127/Ce6 (PCe6-2), were obtained and separated by hydrophobic interaction chromatography. In this study, PCe6-1 was employed because it has good solubility in aqueous media. The singlet oxygen generation (SOG) efficiency and fluorescence activity of PCe6-1 in aqueous media dramatically increased compared to free Ce6. Moreover, confocal imaging and fluorescence-activated cell sorting (FACS) analysis confirmed its enhanced internalization rate in mouse colon tumor (CT-26) cells. After light irradiation, the cellular phototoxicity of PCe6-1 against CT-26 was approximately 3 times higher than that of free Ce6 in vitro. Furthermore, PCe6-1 exhibited enhanced tumor-specific distribution and tumor growth inhibition after intravenous injection into tumor-bearing mice. These results suggest that PCe6-1 is a good candidate as a photosensitizer due to its high cellular internalization rate and tumor targeting efficiency.
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Hyung
authors.initials: H
authors.lastname: Park
authors.forename: Kun
authors.initials: K
authors.lastname: Na
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D005434:Flow Cytometry; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D020442:Poloxamer / Q000737:chemistry* / Q000627:therapeutic use*; D011166:Porphyrins / Q000737:chemistry* / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000627:therapeutic use*; D026082:Singlet Oxygen / Q000378:metabolism
chemical_list: D002735:Chlorophyllides; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D020442:Poloxamer; D026082:Singlet Oxygen; C062985:phytochlorin