title: Obtaining control of cell surface functionalizations via Pre-targeting and Supramolecular host guest interactions.
abstract: The use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or "training" of cells to make them suitable for a specific application remains complex. By envisioning a chemical toolbox that enables specific, but straight-forward and generic cellular functionalization, we investigated how membrane-receptor (pre)targeting could be combined with supramolecular host-guest interactions based on β-cyclodextrin (CD) and adamantane (Ad). The feasibility of this approach was studied in cells with membranous overexpression of the chemokine receptor 4 (CXCR4). By combining specific targeting of CXCR4, using an adamantane (Ad)-functionalized Ac-TZ14011 peptide (guest; KD= 56 nM), with multivalent host molecules that entailed fluorescent β-CD-Poly(isobutylene-alt-maleic-anhydride)-polymers with different fluorescent colors and number of functionalities, host-guest cell-surface modifications could be studied in detail. A second set of Ad-functionalized entities enabled introduction of additional surface functionalities. In addition, the attraction between CD and Ad could be used to drive cell-cell interactions. Combined we have shown that supramolecular interactions, that are based on specific targeting of an overexpressed membrane-receptor, allow specific and stable, yet reversible, surface functionalization of viable cells and how this approach can be used to influence the interaction between cells and their surroundings.
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Mark T M
authors.initials: MT
authors.lastname: Rood
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Silvia J
authors.initials: SJ
authors.lastname: Spa
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Mick M
authors.initials: MM
authors.lastname: Welling
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.|Laboratory of BioNanoTechnology, Axis, Building 118, Bornse weilanden 9, 6708 WG Wageningen, The Netherlands.
authors.forename: Jan Bart
authors.initials: JB
authors.lastname: Ten Hove
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Danny M
authors.initials: DM
authors.lastname: van Willigen
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Tessa
authors.initials: T
authors.lastname: Buckle
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.|Laboratory of BioNanoTechnology, Axis, Building 118, Bornse weilanden 9, 6708 WG Wageningen, The Netherlands.
authors.forename: Aldrik H
authors.initials: AH
authors.lastname: Velders
authors.affiliation: Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Albinusdreef 2, PO BOX 9600, 2300 RC, Leiden, The Netherlands.|Laboratory of BioNanoTechnology, Axis, Building 118, Bornse weilanden 9, 6708 WG Wageningen, The Netherlands.
authors.forename: Fijs W B
authors.initials: FW
authors.lastname: van Leeuwen
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008299:Maleic Anhydrides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: C527276:CXCR4 protein, human; D005456:Fluorescent Dyes; D008299:Maleic Anhydrides; D010456:Peptides, Cyclic; D011108:Polymers; D019718:Receptors, CXCR4; D047392:beta-Cyclodextrins; C000609390:poly(isobutylene-alt-maleic anhydride); D000218:Adamantane