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A Multifunctional Lipid-Based Nanodevice for the Highly Specific Codelivery of Sorafenib and Midkine siRNA to Hepatic Cancer Cells
journal contribution
posted on 2019-08-22, 20:43 authored by Mahmoud
A. Younis, Ikramy A. Khalil, Mahmoud M. Abd Elwakil, Hideyoshi HarashimaHepatocellular
carcinoma (HCC), a common deadly malignancy, requires
novel therapeutic strategies to improve the survival rate. Combining
chemotherapy and gene therapy is a promising approach for increasing
efficiency and reducing side effects. We report on the design of highly
specific lipid nanoparticles (LNPs) encapsulating both the chemotherapeutic
drug, sorafenib (SOR), and siRNA against the midkine gene (MK), thereby
conferring a novel highly efficient anticancer effect on HCC. The
LNPs were modified with a targeting peptide, SP94, which is selective
for hepatic cancer cells (HCCs), thus permitting the specific delivery
of the payload. MK-siRNA increased the sensitivity of HCCs, HepG2,
to SOR (IC50 for SOR+MK-siRNA: 5 ± 1.50 μM compared
to 9 ± 2.20 and 17 ± 2.60 μM for SOR+control siRNA
and MK-siRNA, respectively). The selectivity was confirmed by cellular
uptake, cytotoxicity, and gene-silencing studies in HCCs, HepG2, and
Hepa 1–6, compared to other cancerous cells, HeLa, and normal
cells, FL83B. The use of a novel pH-sensitive lipid, YSK05, increased
the cytotoxic and gene knockdown efficiencies and limited extracellular
drug release. The nanoparticles were also compatible with serum and
showed no aggregation after long storage. The efficient and specific
codelivery system reported here is a highly promising strategy for
the treatment of HCC.
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Keywords
lipid nanoparticlesanticancer effectMidkine siRNAmidkine geneYSKFL 83Bgene knockdown efficienciesHepatic Cancer Cells Hepatocellular carcinomaside effectsHCCgene-silencing studieschemotherapeutic drugsurvival rateLNPcodelivery systemSPSpecific Codeliverygene therapyIC 50MKnovel pH-sensitive lipidextracellular drug releasehepatic cancer cellsSORMultifunctional Lipid-Based Nanodevice
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