| Popis: |
Chronic inflammation is a significant pathological process found in a range of disease states. Treatments to reduce inflammation in this family of diseases may improve symptoms and disease progression, but are largely limited by variable response rates, cost, and off-target effects. Macrophages are implicated in many inflammatory diseases for their critical role in the maintenance and resolution of inflammation. Macrophages exhibit significant plasticity to direct the inflammatory response by taking on an array of pro- and anti-inflammatory phenotypes based on extracellular cues. One robust anti-inflammatory physiologic cue is the engulfment of apoptotic cells. In this work, we have developed a nanoparticle to target and reduce macrophage-mediated inflammation by mimicking the anti-inflammatory effect of apoptotic cell engulfment. The nanoparticle, comprised of a poly(lactide-co-glycolide) core, is coated in phosphatidylserine (PS)-supplemented cell plasma membrane to emulate key characteristics of the apoptotic cell surface. We demonstrate that this particle can reduce the production of pro-inflammatory cytokines and drive an anti-inflammatory phenotype shift without the use of small molecules or other drugs. We additionally functionalized the particle surface with an acid-sensitive polyethylene glycol (PEG) moiety to increase the delivery of our particles to sites of chronic inflammation in a mouse model. Particles are preferentially taken up by macrophages at the site of inflammation to promote an anti-inflammatory phenotype shift. The development of a nanoparticle to drive this pro-to-anti-inflammatory macrophage phenotype transition, through the use of a physiologic anti-inflammatory pathway, illustrates a new potential strategy in the design of therapeutics for chronic inflammation. |
