title: Targeted thrombolysis by using of magnetic mesoporous silica nanoparticles.
abstract: Thrombolytics inevitably led to the risk of hemorrhagic complications due to their non-specific plasminogen activation in treatment of thrombosis. The aim of this study was to determine whether a kind of superparamagnetic mesoporous silica nanoparticle with expanded pore size could achieve effectively targeted thrombolysis. The magnetic mesoporous silica nanoparticles (M-MSNs) with the pore size of 6 nm were prepared by method of the surfactant templating on nano magnetic particles. We investigated the feasibility and efficacy of target thrombolysis with the resultant spheres through fibrin agarose plate assay (FAPA) and a dynamic flow system in vitro. It displayed a 30-fold enhancement of urokinase (UK) loading capacity over the particles without mesoporous layer or the magnetic spheres with mesopores of 3.7 nm. A sustained release behavior was observed due to its larger pore size, higher surface area and narrow mesopore channals contrast to non-mesoporous and small mesopore of 3.7 nm controls. Meanwhile, fibrin agarose plate assay revealed that UK/M-MSNs exhibited a more rapid growth rate of thrombolysis even lasting for 3 days. Additionally, flow model test in vitro suggested this kind of nanoparticle complex enhanced the thrombolysis efficacy by 3.5 fold over the same amount of native UK in 30 min. When compared to non-mesoporous and small mesopore controls, it also represented an extremely higher lysis efficiency (ANOVA, P < 0.01) and a shorter reperfusion time (ANOVA, P < 0.001). Such a magnetic mesoporous silica nanoparticle carrier was expected to be further studied for targeted thrombolytic therapy.
authors.affiliation: Nano Biomedical Research Center, School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Wang
authors.forename: Jixi
authors.initials: J
authors.lastname: Zhang
authors.forename: Ziming
authors.initials: Z
authors.lastname: Yuan
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Yang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Hongchen
authors.initials: H
authors.lastname: Gu
mesh_terms: D000327:Adsorption; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000008:administration & dosage* / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000188:drug therapy* / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D013501:Surface-Active Agents; D012822:Silicon Dioxide; D014568:Urokinase-Type Plasminogen Activator