Tunable Leuko-polymersomes That Adhere Specifically to Inflammatory Markers
Abstract
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- I under flow. We
find that maximal adhesion occurs at intermediate densities of both sialyl Lewis X
and anti-ICAM- I, 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.
Type
Other articleSubject
intercellular-adhesion molecule-1infrared-emissive polymersomes
cell-adhesion
in-vivo
p-selectin
endothelial-cells
drug-delivery
system
receptors
vesicles
chemistry, multidisciplinary
chemistry, physical
materials science, multidisciplinary
Permalink
https://hdl.handle.net/10161/3993Published Version (Please cite this version)
10.1021/1a1017032Citation
Robbins,Gregory P.;Saunders,Randi L.;Haun,Jered B.;Rawson,Jeff;Therien,Michael J.;Hammer,Daniel
A.. 2010. Tunable Leuko-polymersomes That Adhere Specifically to Inflammatory Markers.
Langmuir 26(17): 14089-14096.
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Show full item recordScholars@Duke
Michael J. Therien
William R. Kenan, Jr. Distinguished Professor of Chemistry
Our research involves the synthesis of compounds, supramolecular assemblies, nano-scale
objects, and electronic materials with unusual ground-and excited-state characteristics,
and interrogating these structures using state-of-the-art transient optical, spectroscopic,
photophysical, and electrochemical methods. Over chemical dimensions that span molecules
to materials, we probe experimental and theoretical aspects of charge migration reactions
and ultrafast electron transfer processes. Insights

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