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 Hanes; Kevin M Shakesheff; Douglas J Goetz

doi:10.1073/pnas.2631433100

Back

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

Journal article

Open access

Peer reviewed

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 Hanes, Kevin M Shakesheff and Douglas J Goetz

Proceedings of the National Academy of Sciences - PNAS, Vol.100(26), pp.15895-15900

12/23/2003

DOI: 10.1073/pnas.2631433100

PMCID: PMC307664

PMID: 14668435

Files and links (1)

url

https://doi.org/10.1073/pnas.2631433100View

Published (Version of record) Open Access

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.

Intercellular Adhesion Molecule-1 - physiology

Vascular Cell Adhesion Molecule-1 - immunology

Intercellular Adhesion Molecule-1 - immunology

Humans

Cells, Cultured

Endothelium, Vascular - physiopathology

Umbilical Veins

E-Selectin - immunology

Vascular Cell Adhesion Molecule-1 - physiology

Antibodies, Monoclonal

Leukocytes - physiology

Inflammation - blood

Endothelium, Vascular - physiology

Microscopy

Cell Adhesion - physiology

E-Selectin - physiology

Inflammation - physiopathology

Leukocytes - cytology

Details

Title: Subtitle: Leukocyte-inspired biodegradable particles that selectively and avidly adhere to inflamed endothelium in vitro and in vivo
Creators: Harshad S Sakhalkar - Departments of Chemical Engineering and Biological Sciences, Ohio University, Athens, OH 45701, USA
Milind K Dalal
Aliasger K Salem
Ramin Ansari
Jie Fu
Mohammad F Kiani
David T Kurjiaka
Justin Hanes
Kevin M Shakesheff
Douglas J Goetz
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.100(26), pp.15895-15900
DOI: 10.1073/pnas.2631433100
PMID: 14668435
PMCID: PMC307664
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: United States
Language: English
Date published: 12/23/2003
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9983985716002771

Metrics

18 Record Views

157 Times Cited - Web of Science