Chitosan based pH-responsive polymeric prodrug vector for enhanced tumor targeted co-delivery of doxorubicin and siRNA

The synthesis of GA-CS-HBA-DOX@siRNA and the pH-responsive release. • A chitosan-based pH-responsive polymeric prodrug co-delivery system was developed. • This carrier can efficiently transfer doxorubicin and Bcl-2 siRNA to liver cancer. • The hydrazone bond promoted the pH-responsive release of doxorubicin and siRNA. • This carrier can enhance the synergistic efficacy of gene-chemotherapies. The co-delivery of chemotherapeutic drugs and siRNA has gained increasing attentions owing to the enhanced antitumor efficacy over single administration. In this work, a chitosan-based pH-responsive prodrug vector was developed for the co-delivery of doxorubicin (DOX) and Bcl-2 siRNA. The accumulation of fabricated nanoparticles in hepatoma cells was enhanced by glycyrrhetinic acid receptor-mediated endocytosis. The cumulative release amount of the encapsulated DOX and siRNA reached 90.2 % and 81.3 % in 10 h, respectively. More strikingly, this nanoplatform can efficiently integrate gene- and chemo-therapies with a dramatically enhanced tumor inhibitory rate (88.0 %) in vivo. This co-delivery system may provide the latest strategy to meet the needs of combination therapies for tumors, offering safe and efficient improvements to the synergistic antitumor efficacy of gene-chemotherapies.