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Macrocycle-Wrapped Polyethylenimine for Gene Delivery with Reduced Cytotoxicity


Due to its outstanding capability to facilitate DNA condensation, transportation and endosomal escape, polyethylenimine (PEI) has been frequently studied in gene delivery. However, its molecular weight (M.W.) dependent transfection efficiency and cytotoxicity has been a vicious circle that has limited its clinical application. To resolve this dilemma, e.g. a large M.W. PEI (branched, 25 KDa) has a satisfactory transfection efficiency, yet high non-specific cytotoxicity for gene delivery, a supramolecular strategy employing macrocyclic cucurbit[7]uril (CB[7]) was developed for the first time. The successful wrapping PEI by the macrocyclic CB[7] was demonstrated by 1H NMR spectroscopy and supported by isothermal titration calorimetry (ITC) titration. The plasmid DNA (pDNA) condensability of PEI was not affected by the supramolecular coating, as evidenced from the agarose gel electrophoresis assay. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results demonstrated that the particle size, zeta potential, and morphology of the self-assemblies of PEI/pDNA and PEI/CB[7]/pDNA were rather comparable. As a consequence of the supramolecular wrapping, the cytotoxicity of PEI was significantly constrained, as demonstrated by MTT assay, apoptosis assay, and hemolysis study. More importantly, both the cellular uptake and gene transfection efficiency results suggested that the supramolecular wrapping of PEI by CB[7] exhibited negligible effects on PEI as an effective non-viral gene delivery vector. This novel supramolecular-wrapping strategy is providing new insights for facile alleviation of the non-specific toxicity of PEI and potentially other polycationic gene vectors without compromising their transfection efficiency.

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Publication details

The article was received on 06 Jan 2018, accepted on 06 Mar 2018 and first published on 07 Mar 2018

Article type: Paper
DOI: 10.1039/C8BM00022K
Citation: Biomater. Sci., 2018, Accepted Manuscript
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    Macrocycle-Wrapped Polyethylenimine for Gene Delivery with Reduced Cytotoxicity

    Q. Huang, S. Li, Y. Ding, H. Yin, L. Wang and R. Wang, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C8BM00022K

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