title: Bioreducible polyethylenimine nanoparticles for the efficient delivery of nucleic acids.
abstract: Recently, non-viral vectors for nucleic acid delivery have received considerable attention. Among the various non-viral vectors, branched polyethylenimine (bPEI, 25 kDa) has been one of the most widely used carrier systems due to its high transfection efficiency, however, it imparts high cytotoxicity. In this study, we have crosslinked bPEI with a bioreducible linker, 3,3'-dithiodipropionic acid (DTPA), via electrostatic interactions to obtain DTPA crosslinked bPEI (DP) nanoparticles. The crosslinking significantly reduced the cytotoxicity of the nanoparticles. To arrive at the best formulation in terms of nucleic acid transfection, a series of DP nanoparticles were prepared by varying the percentage of crosslinking. The dual action of DTPA, i.e. partial blocking of the charge density as well as crosslinking to convert bPEI into its nanoparticles, did not alter the pDNA condensation ability of the so-formed nanoparticles, rather the strategy favoured the unpackaging of the complexes inside the cells improving the release of pDNA, which resulted in a higher transfection efficiency. All the formulations carried nucleic acids inside the cells and exhibited significantly higher transfection efficiencies than native bPEI and the commercial transfection reagent, Lipofectamine™. Sequential siRNA delivery displayed significant suppression in the target gene expression. All together, the evaluation of the delivery systems demonstrates that the newly synthesized DP NPs are quite promising as non-viral gene carriers.
authors: Nucleic Acids Research Laboratory, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India. pkumar@igib.res.in pkumar@igib.in.
authors: Ruby
authors: R
authors: Bansal
authors: Shweta
authors: S
authors: Tayal
authors: K C
authors: KC
authors: Gupta
authors: Pradeep
authors: P
authors: Kumar
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry; D003851:Deoxyribonucleases / Q000737:chemistry; D015870:Gene Expression; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006493:Heparin / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D009696:Nucleic Acids / Q000737:chemistry*; D010316:Particle Size; D004369:Pentetic Acid / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D055672:Static Electricity; D014162:Transfection; D014867:Water / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D009696:Nucleic Acids; D011108:Polymers; D034741:RNA, Small Interfering; D014867:Water; D049452:Green Fluorescent Proteins; D004369:Pentetic Acid; D011094:Polyethyleneimine; D006493:Heparin; D003851:Deoxyribonucleases