Jump to main content
Jump to site search

Macrocycle-wrapped polyethylenimine for gene delivery with reduced cytotoxicity

Author affiliations


Due to its outstanding capability to facilitate DNA condensation, transportation and endosomal escape, polyethylenimine (PEI) has been frequently studied for gene delivery. However, its molecular weight (M.W.) dependent transfection efficiency and cytotoxicity has severely limited its clinical application. To resolve this dilemma, a supramolecular strategy was developed for the first time, in which PEI with large M.W. (branched, 25 kDa) that has a satisfactory transfection efficiency, yet high non-specific cytotoxicity for gene delivery was wrapped with macrocyclic cucurbit[7]uril (CB[7]). The successful wrapping of the PEI by the macrocyclic CB[7] was proved by 1H NMR spectroscopy and supported by isothermal titration calorimetry (ITC). 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 comparable. As a consequence of the supramolecular wrapping, the cytotoxicity of PEI was significantly constrained as demonstrated by MTT assay, apoptosis assay, and a hemolysis study. In particular, both the cellular uptake and the gene transfection efficiency results suggest that the supramolecular wrapping of PEI by CB[7] exhibits negligible effects on PEI, thus functioning as an effective non-viral gene delivery vector. This novel supramolecular-wrapping strategy provides new insights for facile alleviation of the non-specific toxicity of PEI and potentially other polycationic gene vectors without compromising their transfection efficiency.

Graphical abstract: Macrocycle-wrapped polyethylenimine for gene delivery with reduced cytotoxicity

Back to tab navigation

Supplementary files

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, Advance Article
  •   Request permissions

    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, Advance Article , DOI: 10.1039/C8BM00022K

Search articles by author