Targeted Nanoparticles Cure Chronic Inflammatory Diseases in Mouse Models

Nanoparticles containing an anti-inflammatory peptide derived from the protein annexin I and targeted for binding to collagen IV were shown to resolve chronic inflammatory conditions in mouse models.

Investigators at Columbia University (New York, NY, USA) prepared nanoparticles from biodegradable diblock poly(lactic-co-glycolic acid)-b-polyethyleneglycol and poly(lactic-co-glycolic acid)-b-polyethyleneglycol. These particles were loaded with a 24-amino-acid peptide, Ac2-26, which was derived from annexin A1. Annexin A1 belongs to the annexin family of Ca2+-dependent phospholipid-binding proteins that are preferentially located on the cytosolic face of the plasma membrane. Annexin A1 protein, which has an apparent relative molecular mass of 40 kDa, has phospholipase A2 inhibitory activity. Since phospholipase A2 is required for the biosynthesis of prostaglandins and leukotrienes (both potent mediators of inflammation), annexin I may have potential anti-inflammatory activity.

A further refinement allowed the nanoparticles to be specifically targeted to collagen IV, a protein found in abundance at sites of tissue injury. These nanoparticles were administered to a group of mice with self-limited zymosan-induced peritonitis and to another group with hind-limb ischemia-reperfusion injury.

Results reported in the March 26, 2013, online edition of the journal Proceedings of the National Academies of Sciences of the United States of America (PNAS) revealed that intravenous administration of the Ac2-26-containing nanoparticles to mice with peritonitis was significantly more effective at limiting recruitment of neutrophils and at increasing the resolution of inflammation than was intravenous administration of unbound Ac2-26. In mice with reperfusion injury, the nanoparticles reduced tissue damage in comparison with either of two types of control nanoparticles: those with a dud peptide in which the 24 amino acids were scrambled to render it biologically inactive and Ac2-26 nanoparticles without the collagen IV-targeting component.

“A variety of medications can be used to control inflammation. Such treatments, however, usually have significant side effects and dampen the positive aspects of the inflammatory response,” said contributing author Dr. Ira Tabas, professor of pathology and cell biology at Columbia University. “The beauty of this approach is that, unlike many other anti-inflammatory approaches, it takes advantage of nature's own design for preventing inflammation-induced damage, which does not compromise host defense and promotes tissue repair.”

The investigators have filed for patent protection for Ac2-26 nanoparticles to treat a variety of chronic inflammatory conditions, including atherosclerosis, autoimmune diseases, type II diabetes, and Alzheimer's disease.

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