HIF1α-siRNA and gemcitabine combination-based GE-11 peptide antibody-targeted nanomedicine for enhanced therapeutic efficacy in pancreatic cancers

Abstract

Pancreatic cancer is one of the deadliest cancers across the world with an average 5-year survival rate of less than <6%. In this study, gemcitabine (GEM) and HIF1α-siRNA loaded GE-11 peptide conjugated liposome was successfully prepared and evaluated for its antitumor efficacy in pancreatic cancer cells. The GE11 increased the targeting specificity of liposome carrier and increased the intracellular concentrations in the cancer cells. Furthermore, synergistic combination of GEM and HIF1a-siRNA exhibited remarkable improvement in the declining of cancer cell proliferations. siRNA could effectively decrease the expression of HIF1a gene in the cancer cells. Importantly, GE-11 peptide-conjugated GEM/siRNA-loaded liposomes (GE-GML/siRNA) increased the total amount of apoptosis cells with higher proportion of cells in late apoptosis phase. GE-GML induced remarkable apoptosis of cancer cells and induced chromatin condensation and nuclear fragmentation which are considered to be typical features of apoptosis and cell death. GE-GML/siRNA showed a significant reduction in the tumour burden suggesting the superior anticancer efficacy of this formulation. GE-GML/siRNA showed four-fold reduction in tumour compared to control and two-fold reduction compared to GE-GML, respectively. Overall, present work lays foundation for the combination of GEM and HIF1a-siRNA loaded in a targeted nanocarrier system as a unique therapeutic option in pancreatic cancer treatment.

Keywords:

• Gemcitabine
• HIF1α-siRNA
• liposome
• pancreatic cancer
• antitumor efficacy

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported in part by the State Key Program of National Natural Science Foundation of China (No. 8143000311); The National Natural Science Foundation of China (Nos. 81660103 and 81771674); 111 Project (D17011); Guangxi BaGui Scholars; The Natural Science Foundation of Guangxi Province (2015GXNSFFA139004).