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Macrocycle-wrapped polyethylenimine for gene delivery with reduced cytotoxicity
Huang, Qiaoxian1; Li, Shengke1; Ding, Yuan-Fu1,2; Yin, Hang1; Wang, Lian-Hui2; Wang, Ruibing1

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 H-1 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 supra-molecular-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.

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Indexed BySCIE
WOS Research AreaMaterials Science
WOS SubjectMaterials Science, bioMaterials
WOS IDWOS:000431111600011
The Source to ArticleWOS
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Cited Times [WOS]:23   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorWang, Ruibing
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China.
2.Key Laboratory for Organic Electronics and Information Displays, Institute of Advanced Materials, Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing 210046, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Huang, Qiaoxian,Li, Shengke,Ding, Yuan-Fu,et al. Macrocycle-wrapped polyethylenimine for gene delivery with reduced cytotoxicity[J]. BIOMATERIALS SCIENCE,2018,6(5):1031-1039.
APA Huang, Qiaoxian,Li, Shengke,Ding, Yuan-Fu,Yin, Hang,Wang, Lian-Hui,&Wang, Ruibing.(2018).Macrocycle-wrapped polyethylenimine for gene delivery with reduced cytotoxicity.BIOMATERIALS SCIENCE,6(5),1031-1039.
MLA Huang, Qiaoxian,et al."Macrocycle-wrapped polyethylenimine for gene delivery with reduced cytotoxicity".BIOMATERIALS SCIENCE 6.5(2018):1031-1039.
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