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

Scholars@Duke

Therien

Michael J. Therien

William R. Kenan, Jr. Distinguished Professor of Chemistry

Our research involves the synthesis of compounds, supermolecular 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. Research activities span physical inorganic chemistry, physical organic chemistry, synthetic chemistry, bioinorganic chemistry, spectroscopy, photophysics, excited-state dynamics, spintronics, and imaging. My laboratory: (i) designs chromophores and supermolecules that display exceptional opto-electronic properties and elucidates their excited-state dynamics, (ii) engineers highly conjugated molecular structures for optical limiting, specialized emission, and high charge mobility, (iii) designs conjugated materials and hybrid molecular-nanoscale structures for energy conversion reactions, (iv) develops molecular wires that propagate spin-polarized currents, (v) fabricates emissive nanoscale structures for in vivo optical imaging, (vi) engineers de novo transition metal cofactor-binding proteins that test light-driven biological energy transducing mechanisms and realize opto-electronic functionalities not found in nature, and (vii) designs and interrogates complex molecular and nanoscale assemblies in which ultrafast energy and charge migration reactions are controlled by quantum coherence effects.


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