Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep39908
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Funding
- European Research Council (ERC) under the European Union's Seventh Framework Program FP7 [2012-306890]
- NWO [STW 11435]
- Netherlands Organization for Scientific Research STW-VIDI grant [STW BGT11272]
- Society of Nuclear Medicine and Molecular imaging (SNMMI)
- Education and Research Foundation for Nuclear Medicine and Molecular Imaging
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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 beta-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; K-D = 56 nM), with multivalent host molecules that entailed fluorescent beta-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.
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