Science：溶解阻塞血管的药物输送系统可减少副作用

研究人员设计了一种会模仿血小板行为并特别以一种溶解堵塞血管的阻塞的药物作为标靶的新的药物输送系统。受到血小板会被吸引到流体剪力高的地方并会自然迁移到狭窄的血管这一事实的启发，Netanel Korin及其同事给纳米颗粒团块裹了层可溶解阻塞的被称作组织型纤溶酶原激活物或tPA的药物，这些纳米颗粒被设计成会在这种情况下崩裂。相关研究成果刊登在国际杂志Science上。

其结果是形成一种被吸引至身体血管中高流体剪力处的药物输送系统，并在剪力达到某一点时会崩解并释放出裹有tPA层的纳米颗粒。研究人员对有血块的小鼠测试了他们的新的药物输送系统并发现该系统能够在这些啮齿动物中恢复正常的血流，而所用的tPA量则低于正常所需的量。这一发现是重要的，因为在没有这一输送系统的情况下而将tPA施于血液，常常会导致诸如过度出血等有害的副作用。

像维可牢和壁虎胶一样，这种新的以阻塞为标靶的机制是一个“生物启发”设计的例子。而且，虽然它还没有做好用于临床的准备，但对该药进行进一步的优化可能改善对该威胁生命疾病的治疗。

doi:10.1126/science.1217815
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Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels

Netanel Korin1, Mathumai Kanapathipillai1, Benjamin D. Matthews2,3, Marilena Crescente4,5, Alexander Brill4,5, Tadanori Mammoto2, Kaustabh Ghosh2, Samuel Jurek2, Sidi A. Bencherif1,6, Deen Bhatta6, Ahmet U. Coskun7, Charles L. Feldman8, Denisa D. Wagner4,5, Donald E. Ingber1,2,6,*

Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death world-wide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism – in the same way platelets do–to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.