title: Versatile Supramolecular Gene Vector Based on Host-Guest Interaction.
abstract: It is a great challenge to arrange multiple functional components into one gene vector system to overcome the extra- and intracellular obstacles for gene therapy. In this study, we developed a supramolecular approach for constructing a versatile gene delivery system composed of adamantyl-terminated functional polymers and a β-cyclodextrin based polymer. Adamantyl-functionalized low molecular weight PEIs (PEI-Ad) and PEG (Ad-PEG) as well as poly(β-cyclodextrin) (PCD) were synthesized by one-step chemical reactions. The supramolecular inclusion complex formed from PCD to assemble LMW PEI-Ad4 via host-guest interactions can condense plasmid DNA to form nanopolyplexes by electrostatic interactions. The supramolecular polyplexes can be further PEGylated with Ad-PEG to form inclusion complexes, which showed increased salt and serum stability. In vitro experiments revealed that these supramolecular assembly polyplexes had good cytocompatibility and showed high transfection activity close to that of the commercial ExGen 500 at high dose of DNA. Also, the supramolecular vector system exhibited about 60% silencing efficiency as a siRNA vector. Thus, a versatile effective supramolecular gene vector based on host-guest complexes was fabricated with good cytocompatbility and transfection activity.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University , Wuhan 430072, P. R. China.|Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , 3584 CG Utrecht, The Netherlands.|Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430022, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , 3584 CG Utrecht, The Netherlands.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , 3584 CG Utrecht, The Netherlands.
authors.forename: Mies J
authors.initials: MJ
authors.lastname: van Steenbergen
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University , Wuhan 430072, P. R. China.
authors.forename: Renxi
authors.initials: R
authors.lastname: Zhuo
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University , Wuhan 430072, P. R. China.
authors.forename: Xulin
authors.initials: X
authors.lastname: Jiang
mesh_terms: D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans