Polyethylenimine-based nanovector grafted with mannitol moieties to achieve effective gene delivery and transfection
- 7 August 2020
- journal article
- research article
- Published by IOP Publishing in Nanotechnology
- Vol. 31 (32), 325101
- https://doi.org/10.1088/1361-6528/ab8c76
Abstract
Polyethylenimine (PEI), a kind of cationic non-viral gene delivery vector, is capable of stable and efficient transgene expression for gene delivery. However, low transfection efficiency in vivo along with high toxicity limited the further application of gene therapy in the clinic. To enhance gene transfection performance and reduce cytotoxicity of polyethylenimine, branched polyethylenimine-derived cationic polymers BPEI25 k-man-S/L/M/H with different grafting degree with mannitol moieties were prepared and the transfection efficiency was evaluated. Among them, BPEI25 k-man-L showed the best transfection efficiency, lower toxicity, and significantly enhanced long-term systemic transgene expression for 96 h in vivo even at a single-dose administration. The results of cellular uptake mechanism and western-blot experiments revealed that the mannitol modification of BPEI25 k induced and up-regulated the phosphorylation of caveolin-1 and thus enhanced the caveolae-mediated cellular uptake. This class of gene delivery system highlights a paradigmatic approach for the development of novel and safe non-viral vectors for gene therapy.Funding Information
- National Natural Science Foundation of China (81702733)
- Natural Science Foundation of Shaanxi Province (2017ZDXM-SF-021)
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