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

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 4 h 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.