Polymeric nanoparticles responsive to intracellular ROS for anticancer drug delivery

[Display omitted] •Three ROS-responsive amphiphilic copolymers were synthesized.•The ROS-sensitivity of the self-assembled copolymers micelles was investigated.•mPEG-poly(ester-thioether) micelles exhibited the best ROS-responsive drug release and in vitro anticancer activity. Thioketal and thioether are moieties used to fabricate reactive oxygen species (ROS)-responsive polymers for drug delivery. In this paper, three amphiphilic copolymers of mPEG-poly(ester-thioether), mPEG-poly(thioketal-ester) and mPEG-poly(thioketal-ester-thioether) were synthesized. The ROS-responsive behaviors of the three copolymers nanoparticles as drug carriers were investigated. The ROS-sensitivity was demonstrated by NMR, DLS, and SEM. mPEG-poly(ester-thioether) nanoparticles exhibited the fastest drug release rate, which possessed the best ROS sensitivity. The in vitro anticancer activity of the DOX-loaded nanoparticles was studied, the results revealed that the mPEG-poly(ester-thioether) nanoparticles showed the most efficient anticancer activity. Notably, all the three ROS-responsive copolymers nanoparticles showed enhanced cellular uptake and anticancer efficacy comparing to the control mPEG-b-PCL nanoparticles.