title: Solid lipid-PEI hybrid nanocarrier: an integrated approach to provide extended, targeted, and safer siRNA therapy of prostate cancer in an all-in-one manner.
abstract: Small-interfering RNA (siRNA) has a high application potential for therapeutic silencing of pathologic or drug-resistance genes. However, although recent research has led to several nonviral nucleic acid delivery systems with encouraging transfection performance, there remains a substantial gap between these systems and an ideal siRNA carrier that can be safely and effectively used for the more complex delivery tasks such as cancer management. We hypothesized that by integrating the high transfection performance of linear polyethylenimine (PEI) with the controlled release properties of solid lipid components, and complementing the resulting lipid-PEI hybrid nanocarrier (LPN) with receptor-targeting capability, multiple limitations of the conventional siRNA carriers would be simultaneously overcome. Data comparing this new hybrid system with the conventional siRNA-PEI polyplexes showed 15 to 21% less loss of siRNA, higher selectivity for prostate cancer cells over noncancerous prostate cells, and significant reduction in both acute and delayed carrier toxicity especially to the noncancerous RWPE1 cells (e.g., 71.2% of LPN-treated cells preserved proliferative capacity versus ≤30.2% in other groups). We further demonstrated sustained intracellular siRNA release from LPNs, which was shown translatable into extended in vitro and in vivo RNA-interference effects for a minimum of one week. Our findings generally support the use of LPN technology to achieve a longer-acting, less toxic, more efficient, and cancer-specific form of siRNA therapy in an "all-in-one" manner. This brings the nonviral siRNA delivery approach one important step closer to its clinical application.
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Xue
authors.forename: Ho-Lun
authors.initials: HL
authors.lastname: Wong
mesh_terms: D004337:Drug Carriers; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D011094:Polyethyleneimine / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D034741:RNA, Small Interfering
chemical_list: D004337:Drug Carriers; D008055:Lipids; D034741:RNA, Small Interfering; D011094:Polyethyleneimine