Development ofpH-responsive cyclodextrin nanoparticles for tumor-specific photodynamic therapy

초록

In this study, we report pH-responsive porous polysaccharide nanoparticles (NPs) for tumor-specific photodynamic therapy. Herein, gamma-cyclodextrin (gamma CD) conjugated with 3-(diethylamino)propylamine (DEAP, as a pH-responsive moiety) and poly(ethylene glycol) (PEG) was used to fabricate gamma CD-(DEAP/PEG) NPs using a self-assembling process with gamma CD and PEG as a hydrophilic segment and DEAP as a hydrophobic segment. These NPs contain rich pore channels, allowing for the facile encapsulation of chlorin e6 (Ce6, as a model drug) via host-guest supramolecular interactions. Furthermore, the DEAP moieties (pK(b) similar to 7.0) in the gamma CD-(DEAP/PEG) NPs could be protonated at weakly acidic pH (pH 6.8) in a tumor environment. This event resulted in the rapid structural destabilization of the host gamma CD-(DEAP/PEG) NPs owing to the protonated DEAP moieties, thereby leading to the extensive release of the phototoxic Ce6 guest. Consequently, the Ce6-loaded gamma CD-(DEAP/PEG) NPs exhibited a significant inhibition of MDA-MB-231 tumor cell growth under light irradiation, demonstrating their potential as a tumor-specific photosensitizing drug carrier.

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