VCAM-targeting lipid platform brings new hope to the treatment of ischemic stroke

Ischemic stroke is a deadly vascular central nervous system disease that causes disability and death worldwide. 1 Anna R. Rolf R. Mark C. Update of the organoprotective properties of xenon and argon: from bench to beside. Intensive Care Med. Exp. 2020; 8: 11 Google Scholar Enzymatic thrombolysis and mechanical thrombectomy are the main treatment strategies for ischemic stroke treatment at present. 2 Barthels D. Das H. Current advances in ischemic stroke research and therapies. Biochim. Biophys. Acta Mol. Basis Dis. 2020; 1866165260 Google Scholar However, neuroprotection against cerebral ischemia-reperfusion injury is critical to improve the quality of life and lifespan of patients. Unfortunately, no neuroprotectants have been successful in clinical trials due to insufficient drug delivery, off-target effects, and intolerable side effects. 3 Benjamin E.J. Blaha M.J. Chiuve S.E. Cushman M. Das S.R. Deo R. de Ferranti S.D. Floyd J. Fornage M. Gillespie C. et al. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017; 135: e146-e603 Google Scholar The blood-brain barrier (BBB) also poses a problem by limiting the amount of drugs that reach the ischemic area. 4 Jinatongthai P. Kongwatcharapong J. Foo C.Y. Phrommintikul A. Nathisuwan S. Thakkinstian A. Reid C.M. Chaiyakunapruk N. Comparative efficacy and safety of reperfusion therapy with fibrinolytic agents in patients with ST-segment elevation myocardial infarction: a systematic review and network meta-analysis. Lancet. 2017; 390: 747-759 Google Scholar Although damage to the BBB can lead to increased permeability and drug penetration in the acute phase of ischemic stroke, this permeability is transient and resolves during the recovery period after ischemic stroke. 5 Kadry H. Noorani B. Cucullo L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS. 2020; 17: 69 Google Scholar In addition, it has remained difficult to target delivery of candidate neuroprotectants to cells within the ischemic penumbra. Multiple cell types, including neurons, endothelial cells, microglia, astrocytes, and neutrophils, are involved in the pathological processes of ischemic stroke and require targeted drug delivery to prevent off-target effects. Therefore, new platforms that can deliver drugs to the ischemic penumbra, target specific cells, selectively release drugs, and improve drug bioavailability are necessary for the treatment of ischemic stroke.