A Multifunctional Lipid-Based Nanodevice for the Highly Specific Codelivery of Sorafenib and Midkine siRNA to Hepatic Cancer Cells

摘要: Hepatocellular carcinoma (HCC), a common deadly malignancy, requires novel therapeutic strategies to improve the survival rate. Combining chemotherapy and gene therapy is promising approach for increasing efficiency reducing side effects. We report on design of highly specific lipid nanoparticles (LNPs) encapsulating both chemotherapeutic drug, sorafenib (SOR), siRNA against midkine (MK), thereby conferring efficient anticancer effect HCC. The LNPs were modified with targeting peptide, SP94, which selective hepatic cancer cells (HCCs), thus permitting delivery payload. MK-siRNA increased sensitivity HCCs, HepG2, SOR (IC50 SOR+MK-siRNA: 5 ± 1.50 μM compared 9 2.20 17 2.60 SOR+control MK-siRNA, respectively). selectivity was confirmed by cellular uptake, cytotoxicity, gene-silencing studies in Hepa 1-6, other cancerous cells, HeLa, normal FL83B. use pH-sensitive lipid, YSK05, cytotoxic knockdown efficiencies limited extracellular drug release. also compatible serum showed no aggregation after long storage. codelivery system reported here strategy treatment