title: Cyclodextrin-based facial amphiphiles: assessing the impact of the hydrophilic-lipophilic balance in the self-assembly, DNA complexation and gene delivery capabilities.
abstract: Exhaustive structure-efficacy relationship studies on nonviral gene delivery systems are often hampered by the ill-defined or polydisperse nature of the formulations. Facial amphiphiles based on rigid cage-type molecular scaffolds offer unique possibilities towards these studies. Taking advantage of regioselective functionalization schemes, we have synthesized a library of cationic cyclodextrin (CD) derivatives combining a range of hydrophilic and lipophilic domains. We have scrutinized how the hydrophilic-lipophilic balance (HLB) around the CD scaffold determines their self-assembly capabilities and the DNA binding and release abilities of the corresponding CD : DNA nanocomplexes (CDplexes). These features have been ultimately correlated with their capabilities to deliver a reporter luciferase-encoding pDNA into COS-7 cells. The ensemble of results demonstrates that fine tuning of the HLB is critical to induce compaction of DNA by the CD-based facial amphiphiles into transfection-productive CDplexes.
authors.affiliation: Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, Américo Vespucio 49, E-41092 Sevilla, Spain. juanmab@iiq.csic.es.
authors.forename: Iris
authors.initials: I
authors.lastname: Pflueger
authors.affiliation: Institut de Chimie Nice, UMR 7272, Université de Nice Sophia Antipolis, CNRS, 28, Avenue de Valrose, F-06108 Nice, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Charrat
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, E-41012 Sevilla, Spain.
authors.forename: Carmen Ortiz
authors.identifier: http://orcid.org/0000-0002-7676-7721
authors.initials: CO
authors.lastname: Mellet
authors.affiliation: Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, Américo Vespucio 49, E-41092 Sevilla, Spain. juanmab@iiq.csic.es.
authors.forename: José M
authors.initials: JM
authors.lastname: García Fernández
authors.affiliation: Institut de Chimie Nice, UMR 7272, Université de Nice Sophia Antipolis, CNRS, 28, Avenue de Valrose, F-06108 Nice, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Di Giorgio
authors.affiliation: Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, Américo Vespucio 49, E-41092 Sevilla, Spain. juanmab@iiq.csic.es.
authors.forename: Juan M
authors.identifier: http://orcid.org/0000-0002-9788-1507
authors.initials: JM
authors.lastname: Benito
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003505:Cyclodextrins / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D004337:Drug Carriers / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D014162:Transfection
chemical_list: D003505:Cyclodextrins; D004337:Drug Carriers; D004247:DNA