Poly(cystine–PCL) based pH/redox dual-responsive nanocarriers for enhanced tumor therapy

Abstract

Functional polymeric drug delivery systems have generated enormous interest due to their excellent features. This paper reports the development of a novel pH and redox dual-sensitive polymer for anticancer paclitaxel (PTX) delivery applications. The polymer was prepared by polycondensation of disulfide bond-containing dimethyl L-cystinate (Cys) and polycaprolactone (PCL) oligomer via a pH-responsive imine bond. Using the nanoprecipitation method, the polymer can be formulated as nanoparticles (poly(Cys–PCL)/PTX NPs) with a diameter less than 100 nm, as measured by TEM and DLS. The NPs release PTX significantly faster at mildly acidic pH and high concentrations of GSH, exhibiting almost no burst release under the physiological conditions of plasma. Notably, the NPs efficiently deliver PTX to the tumor cells, which was more cytotoxic to 4T1 cancer cells than the pure PTX alone. In vivo results reveal an excellent tumor inhibiting ability, good drug tolerability and biosafety of poly(Cys–PCL)/PTX NPs. Overall, the poly(Cys–PCL)/PTX NPs platform may have greater potential in enhancing cancer therapy.