Conjugation of the photosensitizer Chlorin e6 to pluronic F127 for enhanced cellular internalization for photodynamic therapy

To improve the cellular internalization and tumor-specific targeting efficiency of a photosensitizer, Chlorin e6 (Ce6), was conjugated to Pluronic F127 (R) (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. (C) 2013 Elsevier Ltd. All rights reserved.