Endothelial targeting of high-affinity multivalent polymer nanocarriers directed to intercellular adhesion molecule 1

The Journal of Pharmacology and Experimental Therapeutics
Silvia MuroVladimir R Muzykantov

Abstract

Targeting of diagnostic and therapeutic agents to endothelial cells (ECs) provides an avenue to improve treatment of many maladies. For example, intercellular adhesion molecule 1 (ICAM-1), a constitutive endothelial cell adhesion molecule up-regulated in many diseases, is a good determinant for endothelial targeting of therapeutic enzymes and polymer nanocarriers (PNCs) conjugated with anti-ICAM (anti-ICAM/PNCs). However, intrinsic and extrinsic factors that control targeting of anti-ICAM/PNCs to ECs (e.g., anti-ICAM affinity and PNC valency and flow) have not been defined. In this study we tested in vitro and in vivo parameters of targeting to ECs of anti-ICAM/PNCs consisting of either prototype polystyrene or biodegradable poly(lactic-coglycolic) acid polymers (approximately 200 nm diameter spheres carrying approximately 200 anti-ICAM molecules). Anti-ICAM/PNCs, but not control IgG/PNCs 1) rapidly (t1/2 approximately 5 min) and specifically bound to tumor necrosis factor-activated ECs in a dose-dependent manner (Bmax approximately 350 PNC/cell) at both static and physiological shear stress conditions and 2) bound to ECs and accumulated in the pulmonary vasculature after i.v. injection in mice. Anti-ICAM/PNCs displayed markedl...Continue Reading

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Citations

Sep 26, 2008·Cell and Tissue Research·Eric SimoneVladimir Muzykantov
May 11, 2011·Medical & Biological Engineering & Computing·Moon June Kim, Kyehan Rhee
Aug 16, 2011·ACS Nano·Vladimir V ShuvaevVladimir R Muzykantov
Jun 19, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Silvia MuroVladimir R Muzykantov
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Sep 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jin LiuRavi Radhakrishnan
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