iRGD decorated lipid polymer hybrid nanoparticles for targeted co delivery of doxorubicin and sorafenib to enhance anti hepatocellular carcinoma efficacy.
The combination of doxorubicin (DOX) with sorafenib (SOR) has proven an effective strategy to enhance anti hepatocellular carcinoma (HCC) efficacy. However, respective in vivo pharmacokinetic profiles and different endocytosis capacities of these two drugs greatly hinder their current application. Herein, the tumor targeting peptide iRGD decorated lipid polymer hybrid nanoparticles (NPs) with a shell core structure were developed for co delivery of DOX and SOR (DOX+SOR/iRGD NPs) After the drug ratio was optimized, the stabilized DOX+SOR/iRGD NPs were prepared. Through the iRGD integrin recognition, DOX+SOR/iRGD NPs showed synergistic cytotoxicity, pro apoptotic ability and enhanced internalization rate in human liver cancer HepG2 cells. In vivo pharmacokinetic result demonstrated that an extended circulation and bioavailability of DOX+SOR/iRGD NPs than free drugs. More importantly, DOX+SOR/iRGD NPs significantly enhanced antitumor efficiency in HCC xenograft mouse models. Overall, this study describes a promising nanoparticulate drug co delivery strategy to combine clinical anticancer drugs and enhance anti HCC efficacy.
Nanomedicine nanotechnology, biology, and medicine