Co-liposomes of redox-active alkyl-ferrocene modified low MW branched PEI and DOPE for efficacious gene delivery in serum

摘要: Herein, we present six new lipopolymers based on low molecular weight, branched polyethylenimine (BPEI 800 Da) which are hydrophobically modified using ferrocene terminated alkyl tails of variable lengths. The effects degree grafting, spacer length and the redox state in self assembly properties were investigated detail by TEM, AFM, DLS zeta potential measurements. assemblies displayed an oxidation induced increase size aggregates. co-liposomes comprising lipopolymer a helper lipid, 1,2-dioleoyl phosphatidyl ethanolamine (DOPE), showed excellent gene (pDNA) delivery capability serum containing environment two cancer cell lines (HeLa U251 cells). Optimized formulations remarkably higher transfection activity than BPEI (25 kDa) also significantly better commercial reagent, Lipofectamine 2000 as evidenced from both luciferase GFP expression analysis. Oxidation led to drastically reduced levels was substantiated cellular internalization fluorescently labelled pDNA detected confocal microscopy flow cytometry. Moreover, inactive oxidized lipopolyplexes could be turned active exposure ascorbic acid (AA) culture medium during transfection. Endocytosis inhibition experiments that mediated involved clathrin caveolae pathways while routed via caveolae. Cytotoxicity assays revealed no obvious toxicity for range optimized studied. Overall, have exploited PEI-based efficient polymeric carriers whose differential activities harnessed spatial or temporal transfections.