title: Effects of a PEG additive on the biomolecular interactions of self-assembled dendron nanostructures.
abstract: The ability of self-assembling multivalent DNA-binding dendrons to interact with biological targets is modified by co-assembly with two novel low-molecular-weight cholesterol-functionalised PEG units, one based on triethylene glycol (Chol-PEG-3) and one on an octaethylene glycol (Chol-PEG-8). The addition of either PEG lipid affected the co-assembled nanostructure surface charge and size in different ways depending on the structure of the self-assembling DNA-binding dendron. Co-assembly with Chol-PEG-8 enhanced DNA binding, while Chol-PEG-3 inhibited it. Insertion of Chol-PEG-8 into the aggregates modified their ability to cross a model mucus layer, the details of which can be understood in terms of a balance between the mucoadhesivity due to the surface charge of the nanoscale aggregates and that due to the PEG groups. This study demonstrates that the interaction of nanoscale assemblies with biological systems depends on a number of different factors in a sometimes unpredictable way. Given how simply multiple building blocks can be combined by self-assembly, we conclude that self-assembled multivalent systems have great potential for optimisation to maximise their biological and clinical activity.
authors.affiliation: Department of Chemistry, University of York, Heslington, York, YO105DD, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Barnard
authors.forename: Marcelo
authors.initials: M
authors.lastname: Calderon
authors.forename: Ariane
authors.initials: A
authors.lastname: Tschiche
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.forename: David K
authors.initials: DK
authors.lastname: Smith
mesh_terms: D000818:Animals; D001665:Binding Sites; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D013552:Swine
chemical_list: D050091:Dendrimers; D009077:Mucins; C095164:poly(oxyethylene) cholesteryl ether; C028914:triethylene glycol; D011092:Polyethylene Glycols; D004247:DNA; D002784:Cholesterol