Leukocyte-inspired biodegradable particles that selectively and avidly adhere to inflamed endothelium in vitro and in vivo

Harshad S. Sakhalkar, Milind K. Dalal, Aliasger K. Salem, Ramin Ansari, Jie Fu, Mohammad F. Kiani, David T. Kurjiaka, Justin S Hanes, Kevin M. Shakesheff, Douglas J. Goetz

Research output: Contribution to journalArticle

Abstract

We exploited leukocyte-endothelial cell adhesion chemistry to generate biodegradable particles that exhibit highly selective accumulation on inflamed endothelium in vitro and in vivo. Leukocyte-endothelial cell adhesive particles exhibit up to 15-fold higher adhesion to inflamed endothelium, relative to noninflamed endothelium, under in vitro flow conditions similar to that present in blood vessels, a 6-fold higher adhesion to cytokine inflamed endothelium relative to non-cytokine-treated endothelium in vivo, and a 10-fold enhancement in adhesion to trauma-induced inflamed endothelium in vivo due to the addition of a targeting ligand. The leukocyte-inspired particles have adhesion efficiencies similar to that of leukocytes and were shown to target each of the major inducible endothelial cell adhesion molecules (E-selectin, P-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1) that are up-regulated at sites of pathological inflammation. The potential for targeted drug delivery to inflamed endothelium has significant implications for the improved treatment of an array of pathologies, including cardiovascular disease, arthritis, inflammatory bowel disease, and cancer.

Original languageEnglish (US)
Pages (from-to)15895-15900
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number26
DOIs
StatePublished - Dec 23 2003

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Endothelium
Leukocytes
Endothelial Cells
P-Selectin
E-Selectin
Vascular Cell Adhesion Molecule-1
Cell Adhesion Molecules
Intercellular Adhesion Molecule-1
In Vitro Techniques
Inflammatory Bowel Diseases
Cell Adhesion
Adhesives
Arthritis
Blood Vessels
Cardiovascular Diseases
Pathology
Cytokines
Ligands
Inflammation
Wounds and Injuries

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Leukocyte-inspired biodegradable particles that selectively and avidly adhere to inflamed endothelium in vitro and in vivo. / Sakhalkar, Harshad S.; Dalal, Milind K.; Salem, Aliasger K.; Ansari, Ramin; Fu, Jie; Kiani, Mohammad F.; Kurjiaka, David T.; Hanes, Justin S; Shakesheff, Kevin M.; Goetz, Douglas J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 26, 23.12.2003, p. 15895-15900.

Research output: Contribution to journalArticle

Sakhalkar, Harshad S. ; Dalal, Milind K. ; Salem, Aliasger K. ; Ansari, Ramin ; Fu, Jie ; Kiani, Mohammad F. ; Kurjiaka, David T. ; Hanes, Justin S ; Shakesheff, Kevin M. ; Goetz, Douglas J. / Leukocyte-inspired biodegradable particles that selectively and avidly adhere to inflamed endothelium in vitro and in vivo. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 26. pp. 15895-15900.
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