CD47- and Integrin α4/ß1-Comodified-Macrophage-Membrane-Coated Nanoparticles Enable Delivery of Colchicine to Atherosclerotic Plaque.

Atherosclerosis is a chronic inflammatory disease and the major pathological factor of most cardiovascular diseases, leading to ≈1/3 of deaths worldwide. Improving local delivery of anti-inflammatory drugs to the site of atherosclerosis has significant promise to prevent the development of atherosclerotic plaque clinically. Here, a modified-macrophage-membrane-coated nanoparticle drug delivery able to transport colchicine to the atherosclerotic site is reported. This hybrid system efficiently targets endothelial cells under an inflammatory environment while escaping the endocytosis of macrophages. Furthermore, the anti-inflammatory effect of the modified-macrophage-membrane-coated nanoparticles on foam cells is studied. In vivo, the migration of the modified-macrophage-membrane-coated nanoparticles to atherosclerotic lesions is confirmed in a vulnerable atherosclerotic plaque mouse model. Intravenous injections of the hybrid system successfully reduce the lipid plaque load and improve the plaque stability. This strategy provides a potential therapeutic system for the targeted delivery of anti-inflammatory drugs to the atherosclerotic site for the treatment of atherosclerosis in cardiovascular diseases.

Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab.

OBJECTIVE: The impact of present disease-modifying treatments (DMTs) in multiple sclerosis (MS) on nerve injury and reactive astrogliosis is still unclear. Therefore, we studied the effect of natalizumab treatment on the release of 2 brain-specific tissue damage markers into cerebrospinal fluid (CSF) in MS patients. METHODS: CSF samples from 92 patients with relapsing forms of MS were collected in a prospective manner prior to natalizumab treatment and after 6 or 12 months. In 86 cases, natalizumab was used as second-line DMT due to breakthrough of disease activity. The levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were determined using highly sensitive in-house developed enzyme-linked immunosorbent assays. RESULTS: Natalizumab treatment led to a 3-fold reduction of NFL levels, from a mean value of 1,300 (standard deviation [SD], 2,200) to 400 (SD, 270) ng/l (p < 0.001). The later value was not significantly different from that found in healthy control subjects (350 ng/l; SD, 170; n = 28). Subgroup analysis revealed a consistent effect on NFL release, regardless of previous DMT or whether patients had relapses or were in remission within 3 months prior to natalizumab treatment. No differences between pre- and post-treatment levels of GFAP were detected. INTERPRETATION: Our data demonstrate that natalizumab treatment reduces the accumulation of nerve injury in relapsing forms of MS. It is anticipated that highly effective anti-inflammatory treatment can reduce axonal loss, thereby preventing development of permanent neurological disability.

Adhesion molecules in inflammatory bowel disease: therapeutic implications for gut inflammation.

Mucosal endothelium has become one of the major areas of investigation in gut inflammation. It is now well recognised that it plays an active role in the pathogenesis of both forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis, since endothelial cells regulate mucosal immune homeostasis, acting as "gatekeepers", controlling leukocyte accumulation in the interstitial compartment. This process is mediated by leukocyte-endothelial adhesion molecules. This paper reviews the major molecules that mediate leukocyte-endothelial interactions, and summarises the results of the most recent clinical trials targeting adhesion molecules in inflammatory bowel disease.