Linear PEI nanoparticles: efficient pDNA/siRNA carriers in vitro and in vivo

Linear polyethylenimine (lPEI, 25 kDa) nanoparticles' (LPN) series was synthesized by varying percentage of cross-linking with 1,4-butanediol diglycidyl ether (BDE) and their size, surface charge, morphology, pDNA protection/release, cytotoxicity and transfection efficiency were evaluated. Synthesized nanoparticles (NPs) were spherical in shape (size: ∼109 – 235 nm; zeta potential: +38 to +16 mV). These NPs showed increased buffering capacity with increasing percent cross-linking and also exhibited excellent transfection efficiency (i.e., ∼1.3 – 14.7 folds in case of LPN-5) in comparison with lPEI and the commercial transfection agents used in this study. LPN-5 based GFP-specific siRNA delivery resulted in ∼86% suppression of targeted gene expression. These particles were relatively nontoxic in vitro (in cell lines) and in vivo (in Drosophila). In vivo gene expression studies using LPN-5 in Balb/c mice through intravenous injection showed maximum expression of the reporter gene in the spleen. These results together demonstrate the potential of these particles as efficient transfection reagents.From the Clinical EditorThe authors demonstrate a novel method of synthesizing linear PEI nanoparticles to utilize these as transfection agents.

Graphical AbstractA series of lPEI nanoparticles (LPNs) has been synthesized keeping intact the overall amines and cell viability characteristics of lPEI using BDE as a crosslinker. These LPNs exhibited significantly improved transfection efficiency with relatively negligible cytotoxicity compared to bPEI, lPEI and other commercially available transfection reagents both in vitro and in vivo.Figure optionsDownload high-quality image (135 K)Download as PowerPoint slide