Inflammation can be thought of as two separate processes. Acute inflammation is a critical part of survival. But it comes at a price. Unresolved inflammation drives many chronic diseases, from heart disease to autoimmune disorders.
"It's the persistent, exacerbated inflammation that we need to focus on" to fight those diseases, Columbia University's Gabrielle Fredman told BioWorld Today.
But by combining a peptide that can speed the repair response that follows inflammation with a nanoparticle that targets the peptide for delivery to where it is needed most, Fredman and her colleagues have developed a way to speed the end of the inflammatory response, an approach that might be useful for quieting down such persistent, exacerbated inflammation.
Their findings will be published in the online edition of the Proceedings of the National Academy of Sciences the week of March 18, 2013.
The approach is not anti-inflammatory in a classical sense but instead is pro-resolving. Inflammation can be dampened in two ways. The first is to directly stop the inflammatory response, for example, by targeting proinflammatory cytokines.
That approach can be effective, but has two drawbacks. First, it is necessarily immunosuppressive, because the same cytokines that can direct inflammatory responses against plaques in the arteries also signal the presence of bacterial and viral invaders.
Second, inflammation naturally triggers a reparative response. The innate immune system tends to go to Defcon 1 at the slightest provocation; when faced with a microbial invader, "the first thing you do is to bring out the heavy artillery," co-corresponding author Ira Tabas of Columbia University told BioWorld Today. And that artillery does collateral damage to blood vessels and cells.
"It's a price well worth paying" for protection from infection, Tabas said. "But now, you've got to clean up the mess."
The innate immune system does so through several different so-called resolution mediators, which clamp down on the inflammatory response after a while and set off the processes, which heal damaged bystander tissue. Targeting such resolvins is one way to clamp down on inflammation without inflicting harm elsewhere. (See BioWorld Today, Nov. 4, 2009.)
In their work, the team took a peptide, Ac2-26, which acts through the G-protein coupled receptor ALX/FPR2 to resolve inflammation, and encapsulated it in nanoparticles of about 80 nanometers diameter.
Compared to the peptide by itself, the nanoparticles are much more stable in the bloodstream, because they are less visible to the body's mechanisms for clearing proteins. They also contain a binding molecule that targets them specifically to injured tissue, which simultaneously increases their concentration where they are needed and decreases it elsewhere.
The team tested the particles in mice with either inflamed abdominal walls, or tissue and blood vessel damage after a temporary loss of blood flow to their limbs.
The researchers found that the nanoparticles did not block inflammation, but tempered it and sped up its resolution.
The researchers have experience in commercializing research findings – the Massachusetts Institute of Technology's Robert Langer, who is a co-corresponding author, has founded literally dozens of companies, and is an inventor on a patent estate that puts many nanotechnology companies to shame. (See BioWorld Insight, March 4, 2013.)
Omid Farokhzad, of Harvard Medical School, is another co-author who has experience in bringing science to market, as the co-founder of three companies: BIND Biosciences Inc., Selecta Biosciences Inc. and Blend Therapeutics Inc. (See BioWorld Today, Oct. 28, 2011.)
Farokhzad told BioWorld Today that "it's conceivable that the current technology or a variation of it may get licensed and developed by one of the companies that I'm associated with, but it is also conceivable that another company may be interested in this technology."
The latter is somewhat more likely, he added, because although the new findings are nanotechological in their nature, they are not closely related to what his other start-ups are doing, and "for companies to be successful, they need to focus on important and related problems and have a razor sharp strategy."
By whatever means, Farokhzad said, "I hope that it will move forward one way or another and that it can eventually help patients."