pH-sensitive nanoparticles of poly(l-histidine)–poly(lactide-co-glycolide)–tocopheryl polyethylene glycol succinate for anti-tumor drug delivery

[Display omitted] A novel pH-sensitive polymer, poly(l-histidine)–poly(lactide-co-glycolide)–tocopheryl polyethylene glycol succinate (PLH–PLGA–TPGS), was synthesized to design a biocompatible drug delivery system for cancer chemotherapy. The structure of the PLH–PLGA–TPGS copolymer was confirmed by 1H-NMR, FTIR and GPC. The apparent pKa of the PLH–PLGA–TPGS copolymer was calculated to be 6.33 according to the acid–base titration curve. The doxorubicin (DOX)-loaded nanoparticles (PLH–PLGA–TPGS nanoparticles and PLGA–TPGS nanoparticles) and corresponding blank nanoparticles were prepared by a co-solvent evaporation method. The blank PLH–PLGA–TPGS nanoparticles showed an acidic pH-induced increase in particle size. The DOX-loaded nanoparticles based on PLH–PLGA–TPGS showed a pH-triggered drug-release behavior under acidic conditions. The results of in vitro cytotoxicity experiment on MCF-7 and MCF-7/ADR cells showed that the DOX-loaded PLH–PLGA–TPGS nanoparticles resulted in lower cell viability versus the PLGA–TPGS nanoparticles and free DOX solution. Confocal laser scanning microscopy images showed that DOX-loaded PLH–PLGA–TPGS nanoparticles were internalized by MCF-7/ADR cells after 1 and 4h incubation and most of them accumulated in lysosomes to accelerate DOX release under acidic conditions. In summary, the PLH–PLGA–TPGS nanoparticles have great potential to be used as carriers for anti-tumor drug delivery.