Development of pH‐responsive cyclodextrin nanoparticles for tumor‐specific photodynamic therapy

In this study, we report pH‐responsive porous polysaccharide nanoparticles (NPs) for tumor‐specific photodynamic therapy. Herein, γ‐cyclodextrin (γCD) conjugated with 3‐(diethylamino)propylamine (DEAP, as a pH‐responsive moiety) and poly(ethylene glycol) (PEG) was used to fabricate γCD‐(DEAP/PEG) NPs using a self‐assembling process with γCD 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 (pKb ~ 7.0) in the γCD‐(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 γCD‐(DEAP/PEG) NPs owing to the protonated DEAP moieties, thereby leading to the extensive release of the phototoxic Ce6 guest. Consequently, the Ce6‐loaded γCD‐(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.