Supramolecular Host–Guest Pseudocomb Conjugates Composed of Multiple Star Polycations Tied Tunably with a Linear Polycation Backbone for Gene Transfection

• Published in: Bioconjugate chemistry 2013-06, Vol.24 (6), p.1049-1056
• Main Authors: Hu, Y, Chai, M. Y, Yang, W. T, Xu, F. J
• Format: Article
• Language: English
• Subjects: Amantadine - chemistry; beta-Cyclodextrins - chemistry; Binding sites; Cations - chemical synthesis; Cations - chemistry; Cations - pharmacology; Cell Survival - drug effects; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA - chemistry; Dose-Response Relationship, Drug; Ethanolamine - chemistry; Gene Transfer Techniques; Genes; HEK293 Cells; Hep G2 Cells; Humans; Macromolecular Substances - chemical synthesis; Macromolecular Substances - chemistry; Macromolecular Substances - pharmacology; Models, Molecular; Molecular Structure; Molecules; Particle Size; Plasmids; Polymers - chemical synthesis; Polymers - chemistry; Polymers - pharmacology; Structure-Activity Relationship; Surface Properties
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc400115e

A series of novel supramolecular pseudocomb polycations (l-PGEA-Ad/CD-PGEAs) were synthesized by tying multiple low-molecular-weight β-cyclodextrin (CD)-cored, ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) star polymers (CD-PGEAs) with an adamantine-modified linear PGEA (l-PGEA-Ad) backbone via the host–guest interaction. The pseudocomb carriers were studied in terms of their DNA binding capabilities, cytotoxicities, and gene transfection efficiencies in the HepG2 and HEK293 cell lines. The pseudocomb l-PGEA-Ad/CD-PGEAs exhibited better plasmid DNA-condensing abilities than their counterparts, CD-PGEA and l-PGEA. Meanwhile, the pseudocomb carriers displayed low cytotoxicity, similar to CD-PGEA and l-PGEA. Moreover, the gene transfection efficiencies of the pseudocomb carriers were much higher than those of CD-PGEA and l-PGEA at various PGEA nitrogen/DNA phosphate molar ratios. Such supramolecular preparation of pseudocomb gene carriers could provide a flexible approach for adjusting the structure and functionality of supramolecular polymers via the proper use of non-covalent interactions.