RESUMO
OBJECTIVE: To explore the feasibility of the reversal of multidrug resistance in breast cancer using vector-based small interference RNA(siRNA) and to solve the problems of siRNA transient expression and siRNA delivery in vivo. METHODS: Based on the siRNA sequence which was screened in previous studies that could effectively inhibit the expression of MDR1 gene, the expression plasmid was constructed. The siRNA expression plasmid was then encapsulated in new nano-sized stealth cationic liposomes. Pharmacodynamic studies of the liposomes were carried out in vitro and in vivo. RESULTS: The results showed that the cationic liposomes loaded with MDR1 siRNA expression plasmid could effectively inhibit the expression of MDR1 gene both in vitro and in vivo. CONCLUSION: Multi-drug resistance of breast cancer cells is reversed to a great extent by this siRNA-containing cationic liposomes. Nano-sized cationic liposomes are ideal delivery vehicle of siRNA, which could protect the siRNA from degradation and deliver siRNA into the tumor region where it could exert functions.
RESUMO
In order to solve the problem of selection and in vivo delivery problem in siRNA treatment, hepatitis B virus (HBV) HBx gene which could be targeted by siRNA was studied. The siRNA expression plasmid which specific inhibits HBx expression was obtained by in vitro selection via a dual-luciferase plasmid including HBx-Fluc fusion protein expression domain. The selected siRNA expression plasmid was then encapsulated in PEG-modified cationic liposome, which was devoted into pharmacodynamic studies at both cellular and animal level. The results illustrated that the cationic liposome which encapsulated siRNA expression plasmid could effectively inhibit HBx gene expression both in vitro and in vivo.