| We prepared and evaluated a multifunctional envelope-type nano device(MEND) as a liver-targeting and long-circulation carrier for si RNA. MEND is a kind of composite lipid nanoparticles which can improve the efficiency of transfection too. A polymer, GA-PEG-Pp-DOPE, structure of MEND, was synthesized via modifying polyethylene glycol(PEG) with glycyrrhetinic acid(GA), peptide(Pp), dioleoyl phosphoethanolamine(DOPE). The peptide is a substrate of matrix metalloproteinase 2(MMP-2) therein. 1H-NMR and MS was chosen to identify the GA-PEG-Pp-DOPE. MEND was prepared with GA-PEG-Pp-DOPE and cationic phospholipids via filming-rehydration method. The quality of MEND particles were evaluated by shape, particle size, electric potential, encapsulation efficiency(EE) and stability in serum through transmission electron microscope(TEM), zeta-sizer nano instrument, ultrafiltration centrifugation and enzymatic hydrolysis experiment. We study the cell growth inhibition rate and transfection efficiency of si RNA-MEND with liver cancer cells. K-ras-si RNA-MEND was chosen to investigate expression level of K-ras protein, the invasion and metastasis ability of transfected cells. We can confirm the structure of GA-PEG-Pp-DOPE by 1H-NMR and MS. Si RNA-MEND is a globular molecules which has zeta potential of 0.614±0.05 m V, mean diameter of 163.5±20.0 nm, lipid bilayers and fingerprint structure. The EE can be 82.8%. MEND protected si RNA from being degraded by serum as long as 120 h which is 40 times of naked si RNA, and MEND can be degraded by MMP-2 specially. The biological evaluation results suggested that the mean cell growth inhibition was 12.97±1.35%, and the MEND can transfer into cytoplasm with high efficiently. The invasion and metastasis of liver cancer cells could decrease and K-Ras protein express lower than control groups by 78.61 times after the transfection of K-Ras-si RNA-MEND. MEND, easy to prepare, has high protection and transfection efficiency. |
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