A Small Step Forward

A microparticle is a bubblelike vesicle, smaller than a micrometer, that is released by the endothelial cells that line blood vessels and red and white blood cells. Scientists have begun to crack into the various microparticles to better characterize their biochemical cargo and thus biological functions. National Institute of Dental and Craniofacial Research (NIDCR) grantees and colleagues report an important new find. They show that microparticles derived from circulating white blood cells called polymorphonuclear (PMN) leukocyte cells taken from inflammatory exudates contain specialized, proresolution lipid mediators that help to halt acute inflammation. The implication being, the microparticles deliver the lipid mediators to signal the inflammatory sites to promote resolution. The finding, however, raised an intriguing possibility. If PMN-derived microparticles are inherently anti-inflammatory and can signal resolution, could these vesicles be employed like Trojan horses to construct and deliver other bioengineered, pro-resolution nanoparticles? If so, the approach would further enhance the resolution phase and mimic the body's own novel healing mechanisms. But because the microparticles are natural occupants of the circulatory system, they would deliver their payload without triggering the toxic side effects that many man-made biomaterials now prompt. To test the idea, the researchers harnessed microparticles from human PMNs and used them to construct nanoparticles that they enriched with either aspirin-triggered resolvin D1 or a lipoxin A4 analog, both well established proresolution lipid mediators. They then administered their novel nanomedicines intravenously to mice with experimentally induced inflammation of a temporomandibular joint (TMJ). In their proof-of-principle study, the scientists found that a dose of just 10 nanograms of microparticle-bearing resolvin D1 and the lipoxin A4 analog protected against TMJ inflammation. The researchers concluded, "These findings indicate that humanized nanoparticles, termed nano-proresolving medicines, are mimetics of endogenous resolving mechanisms, possess potent beneficial bioactions, can reduce nanotoxicity, and offer new therapeutic approaches."
(Source: NIDCR, Science News in Brief, July 8, 2011; Norling LV et al. Cutting edge: Humanized nano-proresolving medicines mimic inflammation-resolution and enhance wound healing. Journal of Immunology. May 15, 2011, Volume 186, Number 10)