TAT-modified redox-sensitive nanoparticles for triggered drug delivery and effective breast cancer therapy

Abstract Tumor cell internalization and controlling drug release are two major biological barriers, which limit the clinical application of chemotherapeutic drugs. To address these obstacles, an effective redox-responsive TAT-DSPE-PEG/PEI-SS-PLA/DOX (shorten as TPSPD) nanoparticle was designed in this paper. Doxorubicin (DOX) was incorporated with polyethylenemine-disulfide bond-polylactic acid (PEI-SS-PLA/DOX) to form the core of nanoparticles, while the TAT peptide modifided-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide-(polyethylene glycol)5000 (TAT-PEG-DSPE) was as the shell. Nanoparticles presented proper particle size and suitable serum stability as well as the long circulation time. Moreover, TPSPD nanoparticles enhanced the cellular uptake rate and realized the controlled drug release at the tumor site. In vivo experiments showed that TPSPD possessed favorable antitumor activity and reduced the systemic toxicity. Altogether, the prepared TPSPD nanoparticle was expected to be a promising strategy in cancer therapy.