Fatty acid-based strategy for efficient brain targeted gene delivery
Abstract
Purpose: To investigate a fatty acid-based strategy for efficient brain targeted gene delivery and to understand mechanism(s) of this small molecule-mediated brain gene delivery strategy. Methods: A series of fatty acids (FAs) were conjugated with polyethylenimine (PEI25k). A near-infrared fluorescence probe, IR820, was used to study in vivo and ex vivo brain targeting ability of these fatty acid-PEI conjugates (FA-PEIs). Brain uptake of FA-PEI25k/rhodamine-6-isothiocyanate (RITC)-labeled DNA nanoparticles was investigated via a fluorescence imaging method. Moreover, pEGFP was used as a model gene to study in vitro and in vivo transfection effect of the ideal FA-PEI25k conjugate. Results: FA modification did not have interference with the complexation between DNA and the PEI25k. The FA-PEI25k conjugates showed excellent brain targeting ability compared with unmodified PEI25k. Among these FA-PEI25k conjugates studied, myristic acid (MC)-PEI25k showed sustained brain distribution profile and higher brain DNA uptake. Furthermore, MC-PEI 25k/pEGFP nanoparticles was able to achieve efficient in vitro and in vivo gene transfection. GFP expression was observed at different brain regions in vivo. Conclusions: These results demonstrated that the small molecule fatty acid, particularly myristic acid-based brain gene delivery strategy, is promising to mediate efficient gene transfection in the brain. © 2013 Springer Science+Business Media New York.