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Loaded Leukosomes: A Smart Bomb to Halt Vascular Inflammation.

Even today, a therapy designed to delay, or completely prevent, the ravages of systemic atherosclerosis remains a holy-grail for translational medicine.1 Since every therapy has a potential downside, an approach to target that therapy with precision to an area and thereby reduce off-target complications of any agent is an essential requirement. A step toward this lofty dream appeared in the report from Boada et al2 in Circulation Research, where the authors used a novel approach to produce leukosomes, biomimetic nanoparticles generated by combining lipids with membrane proteins derived from lipopolysaccharide-stimulated macrophages, to target the inflamed vasculature and inhibit disease pathogenesis. These leukosomes were loaded with rapamycin (LeukoRapa) and delivered for a relatively short therapeutic course (once a day for 7 days) into hypercholesterolemic, ApoE−/−, mice. The authors observed decreased macrophage proliferation in the aorta of Leuko-Rapa–treated animals when compared with vehicle treatment or the systemic administration of rapamycin, the latter of which is known to have undesirable side effects including dyslipidemia and interstitial lung disease.3,4 Moreover, LeukoRapa treatment reduced production of inflammatory cytokines and decreased MMP (matrix metalloproteinase) activity in the atherosclerotic aorta. These results are important, as increased production and activity of MMPs play a key role in arterial remodeling, plaque destabilization, rupture, and atherothrombotic vascular disease.5