Abstract:Objective: This study aims to investigate the construction, characterization, and role of fluorinated polyethylene-imide derivative nanomicelles (SPFT) in gene delivery across the blood-brain barrier (BBB). Methods: PEI-HFAA was synthesized through a chemical reaction between polyethylenimide (PEI) and heptafluorobutyric anhydride (HFAA), followed by amide reaction with sinapic acid (SA) to obtain PEI-HFAA-SA (SPF). Finally, SPFT was obtained by encapsulating polysorbitol 80 (PS80) within SPF. The molecular bonds and elemental composition of SPFT were analyzed using infrared absorption spectroscopy, fluorine NMR, and hydrogen NMR spectroscopy. Dynamic light scattering, agarose condensation assay, and transmission electron microscopy were employed to characterize the hydrodynamic particle size, plasmid adsorption capacity and protection ability, stability, as well as the morphology of the carrier-plasmid complex. The gene transfection efficiency and cytotoxicity of SPFT were investigated in mouse glioma cell line Neuro 2a. C57BL/6J mice were intravenously injected with SPFT carrying GFP expression plasmid to observe its distribution in various tissues/organs and evaluate its effect on gene delivery across the blood-brain barrier. Results: SFPT was synthesized via SA and HFAA modification. SPFT had a hydrodynamic particle size of approximately 170 nm while exhibiting significant loading capacity for plasmids along with effective protection against degradation. In vitro experiments revealed that SPFT possessed excellent transfection ability and biocompatibility. In vivo experiments showed that after tailed vein injection into mice, SPFT accumulated in the brain successfully crossed the blood-brain barrier to deliver gene effectively. Conclusion: These findings indicate that SPFT has the potential as a carrier for delivering plasmids across the blood-brain barrier for gene therapy purposes.