Ischemic stroke is a cerebrovascular disease normally caused by interrupted blood supply to the brain. Ischemia would initiate the cascade reaction consisted of multiple biochemical events in the damaged areas of the brain, where the ischemic cascade eventually leads to cell death and brain infarction. Extensive researches focusing on different stages of the cascade reaction have been conducted with the aim of curing ischemic stroke. However, traditional treatment methods based on antithrombotic therapy and neuroprotective therapy are greatly limited for their poor safety and treatment efficacy. Nanomedicine provides new possibilities for treating stroke as they could improve the pharmacokinetic behavior of drugs in vivo, achieve effective drug accumulation at the target site, enhance the therapeutic effect and meanwhile reduce the side effect. In this review, we comprehensively describe the pathophysiology of stroke, traditional treatment strategies and emerging nanomedicines, summarize the barriers and methods for transporting nanomedicine to the lesions, and illustrate the latest progress of nanomedicine in treating ischemic stroke, with a view to providing a new feasible path for the treatment of cerebral ischemia.
Keywords: AEPO, asialo-erythropoietin; APOE, apolipoprotein E; BBB, blood‒brain barrier; BCECs, brain capillary endothelial cells; Blood‒brain barrier; CAT, catalase; COX-1, cyclooxygenase-1; CXCR-4, C-X-C chemokine receptor type 4; Ce-NPs, ceria nanoparticles; CsA, cyclosporine A; DAMPs, damage-associated molecular patterns; GFs, growth factors; GPIIb/IIIa, glycoprotein IIb/IIIa; HMGB1, high mobility group protein B1; Hb, hemoglobin; ICAM-1, intercellular adhesion molecule-1; IL-1β, interleukin-1β; IL-6, interleukin-6; Ischemic cascade; LFA-1, lymphocyte function-associated antigen-1; LHb, liposomal Hb; MCAO, middle cerebral artery occlusion; MMPs, matrix metalloproteinases; MSC, mesenchymal stem cell; NF-κB, nuclear factor-κB; NGF, nerve growth factor; NMDAR, N-methyl-d-aspartate receptor; NOS, nitric oxide synthase; NPs, nanoparticles; NSCs, neural stem cells; Nanomedicine; Neuroprotectant; PBCA, poly-butylcyanoacrylate; PCMS, poly (chloromethylstyrene); PEG, poly-ethylene-glycol; PEG-PLA, poly (ethylene-glycol)-b-poly (lactide); PLGA NPs, poly (l-lactide-co-glycolide) nanoparticles; PSD-95, postsynaptic density protein-95; PSGL-1, P-selectin glycoprotein ligand-1; RBCs, red blood cells; RES, reticuloendothelial system; RGD, Arg-Gly-Asp; ROS, reactive oxygen species; Reperfusion; SDF-1, stromal cell-derived factor-1; SHp, stroke homing peptide; SOD, superoxide dismutase; SUR1-TRPM4, sulfonylurea receptor 1-transient receptor potential melastatin-4; Stroke; TEMPO, 2,2,6,6-tetramethylpiperidine-1-oxyl; TIA, transient ischemic attack; TNF-α, tumor necrosis factor-α; Thrombolytics; cRGD, cyclic Arg-Gly-Asp; e-PAM-R, arginine-poly-amidoamine ester; iNOS, inducible nitric oxide synthase; miRNAs, microRNAs; nNOS, neuron nitric oxide synthase; siRNA, small interfering RNA.
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