Highly enhanced phototoxicity of chlorin e6-conjugated poly(beta-cyclodextrin) with gas forming capacity at an acidic tumor extracellular pH and its in vitro evaluation

초록

In this study, we report a novel polysaccharidic drug conjugate consisting of poly(beta-cyclodextrin) [poly(beta-CD)] with gas-forming carbonate linkages resulting from the chemical coupling of the hydroxyl groups of poly(beta-CD) and cholesteryl chloroformate (CC) and a photosensitizing drug (chlorin e6: Ce6). This drug conjugate was self-assembled in aqueous solution leading to the production of nanoparticles containing the poly(beta-CD) on the hydrophilic outer shell and CC and Ce6 in the hydrophobic inner core. Cleavage (i.e. the detachment of CC moieties) of the carbonate linkage at a slightly acidic pH (similar to pH 6.5) produced carbon dioxide bubbles. More specifically, the nanoparticles (with autoquenched Ce6 molecules in their core at pH 7.4) were destabilized at pH 6.5, thereby dequenching the Ce6 molecules. These experimental results demonstrate that under light illumination the nanoparticles increased singlet oxygen generation at pH 6.5 compared to pH 7.4 and exhibited a higher phototoxicity for KB tumor cells at pH 6.5 compared to pH 7.4. This approach represents an effective photodynamic therapy for acidic tumors. Copyright (C) 2015 John Wiley & Sons, Ltd.

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