Construction of pH/glutathione responsive chitosan nanoparticles by a self-assembly/self-crosslinking method for photodynamic therapy

A novel pH/glutathione (GSH) multi-responsive chitosan nanoparticles (NPs) material has been successfully designed and prepared by a self-assembly/self-crosslinking method for photodynamic therapy (PDT), which overcomes the shortcomings of traditional photosensitizer carriers, such as poor chemical stability, low loading efficiency and single-responsive photosensitizer release. Amphiphilic sulfhydryl chitosan (SA-CS-NAC) is first prepared by modifying chitosan (CS) with stearic acid (SA) and N-acetyl-L-cysteine (NAC), and then subject to self-assembly and self-crosslinking in the presence of photosensitizer, indocyanine green (ICG), to form the ICG-loaded amphiphilic sulfhydryl chitosan nanoparticles (SA-CS-NAC@ICG NPs). The ICG entrapment efficiency and loading efficiency of the NPs are found to be 95.2% and 27.6%, respectively. The multi-responsive ICG release of the NPs to the low pH and high GSH content of the microenvironment in tumor cells is successfully achieved. Under the laser irradiation, the SA-CS-NAC@ICG NPs produce the amount of reactive oxygen species (ROS) twice of that generated by free ICG under the same conditions. The in vitro cell experiment confirmed the strong cellular uptake ability, low biotoxicity and good tumor inhibition of the NPs. Our work has provided a new strategy for the targeted photosensitizer delivery for PDT.