Nano Biomedical Research Center, School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China.
J Biomed Nanotechnol. 2012 Aug;8(4):624-32. doi: 10.1166/jbn.2012.1416.
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.
溶栓剂不可避免地会导致出血并发症的风险，因为它们在治疗血栓时会导致非特异性的纤溶酶原激活。本研究旨在确定一种具有大孔尺寸的超顺磁介孔硅纳米粒子是否能够有效地实现靶向溶栓。通过纳米磁性粒子上的表面活性剂模板法制备了孔尺寸为 6nm 的磁性介孔硅纳米粒子（M-MSNs）。我们通过纤维蛋白琼脂糖平板试验（FAPA）和体外动态流动系统研究了所得球体进行靶向溶栓的可行性和效果。结果显示，与没有介孔层的颗粒或具有 3.7nm 介孔的磁性颗粒相比，载尿激酶（UK）的能力提高了 30 倍。由于其较大的孔径、较高的表面积和较窄的介孔通道，与非介孔和 3.7nm 的小孔径对照相比，观察到了持续的释放行为。同时，纤维蛋白琼脂糖平板试验表明，即使持续 3 天，UK/M-MSNs 也表现出更快的溶栓增长率。此外，体外流动模型试验表明，与相同数量的天然 UK 相比，这种纳米颗粒复合物在 30 分钟内可将溶栓效果提高 3.5 倍。与非介孔和小孔径对照相比，它还表现出极高的溶解效率（ANOVA，P<0.01）和较短的再灌注时间（ANOVA，P<0.001）。这种磁性介孔硅纳米颗粒载体有望进一步研究用于靶向溶栓治疗。
