RETRACTED ARTICLE: Nanoformulation of Apolipoprotein E3-Tagged Liposomal Nanoparticles for the co-Delivery of KRAS-siRNA and Gemcitabine for Pancreatic Cancer Treatment

• DOI: 10.1007/s11095-020-02949-y
• Publication Date: 2020-11-20T15:16:36Z
• Authors: Fengyong Wang; Zhen Zhang
• Keywords: Male; 0301 basic medicine; Antimetabolites, Antineoplastic; Mice, Inbred BALB C; Drug Compounding; Apolipoprotein E3; Gene Transfer Techniques; Mice, Nude; Apoptosis; Cell Cycle Checkpoints; Combined Modality Therapy; Deoxycytidine; Lipids; 3. Good health; Pancreatic Neoplasms; 03 medical and health sciences; Cell Line, Tumor; Liposomes; Mutation; Animals; Humans; Nanoparticles; Cell Proliferation

KRAS is the most frequently mutated gene in human cancers, and ~ 90% of pancreatic cancers exhibit KRAS mutations. Despite the well-known role of KRAS in malignancies, directly inhibiting KRAS is challenging.In this study, we successfully synthesized apolipoprotein E3-based liposomes for the co-delivery of gemcitabine (GEM) and a small interfering RNA targeting KRAS (KRAS-siRNA) to improve the efficacy of pancreatic cancer treatment.Apolipoprotein E3 self-assembly on the liposome surface led to a substantial increase in its internalization in PANC1 human pancreatic cancer cells. KRAS-siRNA led to downregulated KRAS protein expression and KRAS-dependent carcinogenic pathways, resulting in the inhibition of cell proliferation, cell cycle arrest, increased apoptosis, and suppression of tumor progression. The combination of KRAS-siRNA and GEM induced a synergistic improvement in cell apoptosis and significantly lower cell viability compared with single-agent therapy. The low IC50 value of A3-SGLP might be attributed to potentiation of the anticancer effect of GEM by siRNA-mediated silencing of KRAS mutations, thereby inducing synergistic effects on cancer cells.A3-SGLP led to a marked decrease in the overall tumor burden and did not show any signs of toxicity. Therefore, the combination of KRAS-siRNA and GEM holds great potential for the treatment of pancreatic cancer.