A Synergistic and Efficient Thrombolytic Nanoplatform: A Mechanical Method of Blasting Combined with Thrombolytic Drugs.
A Synergistic and Efficient Thrombolytic Nanoplatform: A Mechanical Method of Blasting Combined with Thrombolytic Drugs.
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协同高效溶栓纳米平台：机械爆破与溶栓药物相结合的方法
DOI：
10.2147/ijn.s382964
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发表时间：
2022
影响因子：
8
通讯作者：
中科院分区：
文献类型：
--
作者：
背景与目的血栓形成是一种常见病，对生命健康构成极大威胁。传统治疗或纳米药物的大多数溶栓效果不够有效或安全。因此，我们设计了一种纳米颗粒（NP）与相转变材料和溶栓药物的组合，以实现有效和安全的溶栓。方法以全氟己烷（PFH）和溶栓药物rtPA为核心，以CREKA多肽为载体，设计了一种血栓纤维蛋白靶向相变纳米粒。在低强度聚焦超声（LIFU）下进行纳米颗粒的相变和超声成像的表征。还探索了体外LIU响应性药物释放。在PFH和rtPA的协同作用下，研究了NPs的有效溶栓能力。体内监测血栓形成和生物安全性也得到了验证。结果PPrC纳米粒子在激光聚焦超声辐照下具有良好的超声成像能力，这与纳米粒子的相变特性有关。CREKA多肽可以有效增加纳米颗粒在血栓上的聚集。在体外静态和动态条件下，PFH的“液-气”转化作用可在血栓部位执行挖掘机的破坏功能，促进rtPA的特异性释放，后续rtPA药物溶栓可进一步充分溶解血栓。体内实验表明，纳米颗粒可以监测血栓的形成，具有良好的溶栓效果，并显着降低出血副作用。治疗后大鼠各项生化指标均在正常范围内。结论机械爆破法结合溶栓药物和PFH、rtPA负载的PPrC纳米粒有望成为血栓监测和治疗的新方法。
Background and Objective Thrombosis is a common disease that poses a great threat to life and health. Most thrombolytic effects of traditional treatments or nanomedicine are not efficient or safe enough. Therefore, we designed a nanoparticle (NP) with a combination of a phase transition material and thrombolytic drugs for efficient and safe thrombolysis. Methods A thrombus fibrin-targeted and phase transition NP was designed and contained perfluorohexane (PFH) and the thrombolytic drug rtPA core, with CREKA polypeptides attached to the shell of the PLGA NPs. Characterization of the phase transition and ultrasound imaging of the NPs was carried out under low-intensity focused ultrasound (LIFU). LIFU-responsive drug release in vitro was also explored. Under the synergistic effect of PFH and rtPA, the efficient thrombolysis ability of the NPs was studied in vitro and in vivo. In vivo monitoring of thrombosis and biosafety were also verified. Results The PPrC NPs had good ultrasound imaging ability under LIFU irradiation and were related to the phase transition characteristics of the NPs. CREKA polypeptides can effectively increase the aggregation of the NPs on thrombi. Under static and dynamic conditions in vitro, the “liquid to gas” transformation effect of PFH can perform the destruction function of the excavator at the thrombus site and promote the specific release of rtPA, and the subsequent rtPA drug thrombolysis can further fully dissolve the thrombus. In vivo experiments showed that the NPs can monitor the formation of thrombi and have good thrombolytic effects, with significantly reduced bleeding side effects. The biochemical indexes of the rats were within normal limits after treatment. Conclusion PPrC NPs loaded with PFH and rtPA combining a mechanical way of blasting with thrombolytic drugs may be a promising new and reliable approach for thrombus monitoring and treatment.
影响因子：
4.6
作者：
Amiri M;Jalali-Javaran M;Haddad R;Ehsani P
通讯作者：
Ehsani P