Breaking the fibrinolytic speed limit with microwheel co-delivery of tissue plasminogen activator and plasminogen.
Breaking the fibrinolytic speed limit with microwheel co-delivery of tissue plasminogen activator and plasminogen.
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DOI：
10.1111/jth.15617
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Neeves KB
中科院分区：
文献类型：
--
作者：
Disharoon D;Trewyn BG;Herson PS;Marr DWM;Neeves KB
可以使用组织纤溶酶原激活剂(TPA)来重建被血栓阻塞的血管中的血流；然而，其疗效受到进入和进入血栓的运输以及其底物纤溶酶原耗尽的限制。为了克服这些速度限制，设计了一种基于微轮(μ轮)的平台来共同传递tPA和纤溶酶原，微轮是一种超顺磁性胶体微珠的轮状组件，可以沿表面高速滚动。通过测定不同浓度的tPA(10-800 nM)和纤溶酶原(1-6μM)对血浆凝块的纤溶作用来确定生化速度极限。合成了生物素化磁性介孔二氧化硅纳米粒子，并将其结合到链霉亲和素包裹的超顺磁性小球上，制成了钉状小球。负载纤溶酶原的镶嵌小球表面固定有tPA。检测微球的纤溶酶原释放和tPA活性。在旋转磁场的作用下，将镶嵌的珠子组装成μ轮，并在微流控装置中测量血浆凝块的纤溶作用。血浆凝块的生化限值为~15μm/m in。纤溶酶原负载，tPA固定的μ车轮以相当于生化速度极限的速度溶解血浆凝块。随着开塞钻运动的增加，μ轮会穿透到凝块中，从而超过生化速度限制(~20μm/分钟)，并实现比50 NM tPA高40倍的裂解速率。通过能够机械工作的微型机器人将固定化的酶及其底物共同输送，有可能靶向并快速溶解机械血栓切除器无法接触到的凝块或全身tPA输送的顽固性。
To reestablish blood flow in vessels occluded by clots, tissue plasminogen activator (tPA) can be used; however, its efficacy is limited by transport to and into a clot and by the depletion of its substrate, plasminogen. To overcome these rate limitations, a platform was designed to co-deliver tPA and plasminogen based on microwheels (μwheels), wheel-like assemblies of superparamagnetic colloidal beads that roll along surfaces at high speeds. The biochemical speed limit was determined by measuring fibrinolysis of plasma clots at varying concentrations of tPA (10-800 nM) and plasminogen (1-6 μM). Biotinylated magnetic mesoporous silica nanoparticles were synthesized and bound to streptavidin coated superparamagnetic beads to make studded beads. Studded beads were loaded with plasminogen tPA was immobilized on their surface. Plasminogen release and tPA activity were measured on the studded beads. Studded beads were assembled into μwheels with rotating magnetic fields and fibrinolysis of plasma clots was measured in a microfluidic device. The biochemical speed limit for plasma clots was ~15 μm/min. Plasminogen loaded, tPA immobilized μwheels lyse plasma clots at rate comparable biochemical speed limit. With the addition of corkscrew motion, μwheels penetrate into clots, thereby exceeding the biochemical speed limit (~20 μm/min) and achieving lysis rates 40-fold higher than 50 nM tPA. Co-delivery of an immobilized enzyme and its substrate via a microbot capable of mechanical work has the potential to target and rapidly lyse clots that are inaccessible by mechanical thrombectomy devices or recalcitrant to systemic tPA delivery.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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作者：
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影响因子：
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