Tunable Leuko-polymersomes That Adhere Specifically to Inflammatory Markers

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2010

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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.

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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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10.1021/1a1017032

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Therien

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 into the structure-property relationships of molecular, nanoscale, and macroscopic materials allow us to fabricate polarizable and hyperpolarizable chromophores, structures for molecular electronics applications, optical limiters, and a wide range of other electrooptic and photonic materials that include novel conducting polymers, structures for solar energy conversion, and new platforms for in vivo optical imaging. Other efforts in our laboratory involve the elaborating de novo electron- and energy-transfer proteins, interrogating catalytic redox reactions, designing catalysts for small molecule activation, and developing new tools to manipulate nanoscale structures.


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