Tunable leuko-polymersomes that adhere specifically to inflammatory markers

The polymersome, a fully synthetic cell mimetic, is a tunable platform for drug delivery vehicles to detect and treat disease (theranostics). Here, we design a leuko-polymersome, a polymersome with the adhesive properties of leukocytes, which can effectively bind to inflammatory sites under flow. We...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1992. - 26(2010), 17 vom: 07. Sept., Seite 14089-96
1. Verfasser: Robbins, Gregory P (VerfasserIn)
Weitere Verfasser: Saunders, Randi L, Haun, Jered B, Rawson, Jeff, Therien, Michael J, Hammer, Daniel A
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2010
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Antibodies Biomarkers Butadienes Drug Carriers Elastomers Ligands Oligosaccharides mehr... P-Selectin Sialyl Lewis X Antigen Intercellular Adhesion Molecule-1 126547-89-5 Polyethylene Glycols 3WJQ0SDW1A polybutadiene 9003-17-2 biocytin G6D6147J22 Lysine K3Z4F929H6
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520 |a The polymersome, a fully synthetic cell mimetic, is a tunable platform for drug delivery vehicles to detect and treat disease (theranostics). Here, we design a leuko-polymersome, a polymersome with the adhesive properties of leukocytes, which can effectively bind to inflammatory sites under flow. We hypothesize that optimal leukocyte adhesion can be recreated with ligands that mimic receptors of the two major leukocyte molecular adhesion pathways, the selectins and the integrins. Polymersomes functionalized with sialyl Lewis X and an antibody against ICAM-1 adhere avidly and selectively to surfaces coated with inflammatory adhesion molecules P-selectin and ICAM-1 under flow. We find that maximal adhesion occurs at intermediate densities of both sialyl Lewis X and anti-ICAM-1, owing to synergistic binding effects between the two ligands. Leuko-polymersomes bearing these two receptor mimetics adhere under physiological shear rates to inflamed endothelium in an in vitro flow chamber at a rate 7.5 times higher than those to uninflamed endothelium. This work clearly demonstrates that polymersomes bearing only a single ligand bind less avidly and with lower selectivity, thus suggesting proper mimicry of leukocyte adhesion requires contributions from both pathways. This work establishes a basis for the design of polymersomes for targeted drug delivery in inflammation 
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650 4 |a Research Support, N.I.H., Extramural 
650 4 |a Research Support, U.S. Gov't, Non-P.H.S. 
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650 7 |a Intercellular Adhesion Molecule-1  |2 NLM 
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700 1 |a Saunders, Randi L  |e verfasserin  |4 aut 
700 1 |a Haun, Jered B  |e verfasserin  |4 aut 
700 1 |a Rawson, Jeff  |e verfasserin  |4 aut 
700 1 |a Therien, Michael J  |e verfasserin  |4 aut 
700 1 |a Hammer, Daniel A  |e verfasserin  |4 aut 
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