Enhanced Fibrinolysis with Magnetically Powered Colloidal Microwheels.
Enhanced Fibrinolysis with Magnetically Powered Colloidal Microwheels.
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DOI：
10.1002/smll.201700954
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Neeves KB
中科院分区：
文献类型：
--
作者：
Tasci TO;Disharoon D;Schoeman RM;Rana K;Herson PS;Marr DWM;Neeves KB
阻塞血管的血栓可以用降解纤维蛋白的纤维蛋白溶解剂来解决，纤维蛋白是在血小板之间和周围形成的聚合物，以提供机械稳定性。然而，纤溶速率通常受到纤溶剂向血栓的运输受限递送和穿透的限制。在这里，这些限制被克服与纤维蛋白溶解组织型纤溶酶原激活剂（tPA）功能化的胶体微轮（μ轮）组件，组装，旋转，平移，并最终通过施加的磁场分解。这些微轮通过递送高局部浓度的tPA以诱导表面溶解，并通过利用螺旋运动，机械地渗透到纤维蛋白凝胶和富含血小板的血栓中以引发大量降解，从而导致快速纤维蛋白溶解。tPA-微轮对血浆来源的纤维蛋白凝胶的纤维蛋白溶解比1 μg mL−1 tPA快5倍。遵循螺旋形轨迹的μ轮也可以在105分钟内穿透在止血的微流体模型中形成的100 μm大小的富含血小板的血栓。这种表面和本体溶解机制与机械作用的独特组合产生了靶向纤维蛋白溶解策略，其可能比仅依赖于扩散的方法显著更快，使其非常适合于不能通过导管移除的小血管或穿透血管中的闭塞。
Thrombi that occlude blood vessels can be resolved with fibrinolytic agents that degrade fibrin, the polymer that forms between and around platelets to provide mechanical stability. Fibrinolysis rates however are often constrained by transport-limited delivery to and penetration of fibrinolytics into the thrombus. Here, these limitations are overcome with colloidal microwheel (μwheel) assemblies functionalized with the fibrinolytic tissue-type plasminogen activator (tPA) that assemble, rotate, translate, and eventually disassemble via applied magnetic fields. These microwheels lead to rapid fibrinolysis by delivering a high local concentration of tPA to induce surface lysis and, by taking advantage of corkscrew motion, mechanically penetrating into fibrin gels and platelet-rich thrombi to initiate bulk degradation. Fibrinolysis of plasma-derived fibrin gels by tPA-microwheels is fivefold faster than with 1 μg mL−1 tPA. μWheels following corkscrew trajectories can also penetrate through 100 μm sized platelet-rich thrombi formed in a microfluidic model of hemostasis in ≈5 min. This unique combination of surface and bulk dissolution mechanisms with mechanical action yields a targeted fibrinolysis strategy that could be significantly faster than approaches relying on diffusion alone, making it well-suited for occlusions in small or penetrating vessels not accessible to catheter-based removal.
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影响因子：
--
作者：
Lyu, S;Sparer, R;Untereker, D
通讯作者：
Untereker, D
影响因子：
2.4
作者：
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影响因子：
20.3
作者：
Pugh, Nicholas;Simpson, Anna M. C.;Farndale, Richard W.
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Farndale, Richard W.
影响因子：
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作者：
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通讯作者：
Zhao, Yiping
DOI：
10.1073/pnas.1407636111
发表时间：
2014-08-05
影响因子：
11.1
作者：
Liu, Bin;Gulino, Marco;Breuer, Kenneth S.
通讯作者：
Breuer, Kenneth S.