Co-liposomes of redox-active alkyl-ferrocene modified low MW branched PEI and DOPE for efficacious gene delivery in serum
Journal of Materials Chemistry B, ISSN: 2050-750X, Vol: 3, Issue: 11, Page: 2318-2330
2015
- 20Citations
- 19Captures
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Metrics Details
- Citations20
- Citation Indexes20
- 20
- CrossRef18
- Captures19
- Readers19
- 19
Article Description
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 of degree of grafting, spacer length and the redox state of ferrocene in the lipopolymers on the self assembly properties were investigated in detail by TEM, AFM, DLS and zeta potential measurements. The assemblies displayed an oxidation induced increase in the size of the aggregates. The co-liposomes comprising the lipopolymer and a helper lipid, 1,2-dioleoyl phosphatidyl ethanolamine (DOPE), showed excellent gene (pDNA) delivery capability in a serum containing environment in two cancer cell lines (HeLa and U251 cells). Optimized formulations showed remarkably higher transfection activity than BPEI (25 kDa) and were also significantly better than a commercial transfection reagent, Lipofectamine 2000 as evidenced from both the luciferase activity and GFP expression analysis. Oxidation of ferrocene in the lipopolymers led to drastically reduced levels of gene transfection which was substantiated by reduced cellular internalization of fluorescently labelled pDNA as detected using confocal microscopy and flow cytometry. Moreover, the transfection inactive oxidized lipopolyplexes could be turned transfection active by exposure to ascorbic acid (AA) in cell culture medium during transfection. Endocytosis inhibition experiments showed that gene expression mediated by reduced formulations involved both clathrin and caveolae mediated pathways while the oxidized formulations were routed via the caveolae. Cytotoxicity assays revealed no obvious toxicity for the lipopolyplexes in the range of optimized transfection levels in both the cell lines studied. Overall, we have exploited the redox activity of ferrocene in branched PEI-based efficient polymeric gene carriers whose differential transfection activities could be harnessed for spatial or temporal cellular transfections.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84924347805&origin=inward; http://dx.doi.org/10.1039/c4tb01771d; http://www.ncbi.nlm.nih.gov/pubmed/32262062; http://xlink.rsc.org/?DOI=C4TB01771D; http://pubs.rsc.org/en/content/articlepdf/2015/TB/C4TB01771D; https://xlink.rsc.org/?DOI=C4TB01771D; https://dx.doi.org/10.1039/c4tb01771d; https://pubs.rsc.org/en/content/articlelanding/2015/tb/c4tb01771d
Royal Society of Chemistry (RSC)
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