Hypoxia/pH dual-responsive nitroimidazole-modified chitosan/rose bengal derivative nanoparticles for enhanced photodynamic anticancer therapy

Abstract Most of the traditional photosensitizers (PSs) used in photodynamic therapy (PDT) have poor tumor targeting and phototoxic side effects. Drug delivery systems can be designed to be triggered to release payload PSs in response to intracellular hypoxia and acidic environment of tumors with controllable photoactivity to achieve enhanced therapeutic effects with minimal side-effects. In this work, we synthesized nitroimidazole-modified chitosan (Cs-NA) and prepared Cs-NA/rose bengal ω-carboxyheptyl ester (a rose bengal derivative, RBD) complex nanoparticles (Cs-NA/RBD) for pH and hypoxia double-responsive RBD delivery. Cs-NA/RBD possessed appropriate particle size of about 86.9 nm and zeta potential of +33.4 mV, showed good stability in cell culture medium, and demonstrated increased accumulative release at acidic and hypoxia condition by about 60% compared to that at neutral pH. The cellular uptake efficiency of Cs-NA/RBD in non-small cell lung cancer PC9 cells increased more than 10 times compared with Cs-NA/RB. The anti-proliferative effects and the generation of reactive oxygen species (ROS) in PC9 cells indicated the notable photodynamic therapeutic effects of Cs-NA/RBD. These results suggested that Cs-NA/RBD could be a promising nanoplatform for enhanced controllable photodynamic anticancer therapy.