Benzamide analogue-conjugated polyethylenimine for brain-targeting and gene delivery

In this study, a small molecule, benzamide analogue, p-hydroxybenzoic acid (p-HA), was used as a novel ligand for brain-targeting gene delivery. p-HA was conjugated to polyethylenimine and further labeled with a near infrared dye, IR820, for in vivo and ex vivo imaging study. Significant fluorescent signal was detected in brain from 0.5 to 24 h after injection compared with unmodified PEI. Then nanoparticles were prepared with p-HA-PEI to encapsulate pEGFP and pGL2 as reporter genes and characterized on the cell level. In 5y cells green fluorescent protein expression could be observed by fluorescent microscopy and significant higher expression of firefly luciferase was detected in p-HA-PEI/pGL2 group than in PEI/pGL2 group. For in vivo gene expression study, comparable high expression of green fluorescent protein in brain sections was confirmed using both confocal fluorescent microscopy and in vivo fluorescent imaging. All these results suggested that p-HA-PEI could be potentially used for brain targeted gene delivery.