pH/redox dual response nanoparticles with poly-γ-glutamic acid for enhanced intracellular drug delivery

Abstract Stimuli-responsive nanomaterials drug delivery systems have attracted much attention owing to the ability to deliver drugs to designated locations especially for tumor cells. Here, positively and negatively charged pH/redox dual stimuli-responsive nanoparticles (NPs) were prepared with biocompatible poly-γ-glutamic acid (γ-PGA), cysteine (Cys), and chitosan (CS) through amide bond and electrostatic interactions. These nanocarriers (γ-PGA-S-S-CS NPs) were used to load the anticancer drug doxorubicin (DOX) to reduce toxicity to normal cells and increase uptake by tumor cells. The drug-loaded nanoparticles γ-PGA-S-S-CS-DOX NPs were characterized via DLS, XRD, FT-IR and TEM techniques. The DOX was released from γ-PGA-S-S-CS-DOX NPs under an acidic and redox environment, while the nanoparticles were kept stable under physiological conditions. in vitro cytotoxicity studies showed that the drug carriers do not impair the growth of cells, and cellular uptake experiments indicated that the drug-loaded NPs were taken up easily by tumor cells compared with the free drug. The results suggested that the dual response nanosystem carrier can be applied to the targeted delivery of other drugs in the cancer field.