Near-Infrared Triggered Release of uPA from Nanospheres for Localized Hyperthermia-Enhanced Thrombolysis
Near-Infrared Triggered Release of uPA from Nanospheres for Localized Hyperthermia-Enhanced Thrombolysis
复制标题
近红外触发纳米球释放 uPA 用于局部热疗增强溶栓
DOI：
10.1002/adfm.201701824
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发表时间：
2017-10-26
影响因子：
19
通讯作者：
Ding, Xingwei
中科院分区：
文献类型：
--
作者：
Wang, Xiaolei;Wei, Chaochao;Ding, Xingwei
目前，大多数溶栓药物存在循环时间短、临床治疗所需剂量过大等局限性，增加了发生颅内出血的致死性风险。在这里，一个近红外触发的控释系统，使用金@介孔二氧化硅核壳纳米球(Au@MSNS)和相变材料1-十四醇，被设计成按需释放尿激酶型纤溶酶原激活剂(UPA)。由于Au@MSNS诱导的光热效应引起的温度升高，所制备的体系提供了释放uPA的灵敏体系。为了进行体外研究，设计并制作了3D打印的静脉血管系统，以模拟系统在血管中的溶栓过程。建立小鼠尾部血栓模型，评价体内溶栓效果。因此，局部热疗对溶栓有有效的增强作用。因此，根据实验结果，制备的系统显示出两个方面的潜在优势：减少副作用风险的uPA受控释放和减少药物用量的局部高温增强溶栓。该制剂在热溶栓的辅助下，具有高效、按需释放药物的特点，是一种更安全的溶栓治疗方案，符合精密医学的发展趋势。
Currently, most thrombolytic agents are limited by short circulation time and excessive dose needed for clinical therapy, which increases lethal risk for intracranial hemorrhage. Here, a near-infrared-triggered, controlled-release system, using gold@mesoporous silica core-shell nanospheres (Au@MSNs) with phase-changed material 1-tetradecanol, is formulated to release urokinase plasminogen activators (uPA) on demand. The prepared system presents a sensitive system for releasing uPA, owing to an elevated temperature created by Au@MSNs-induced photothermal effect. For in vitro study, a 3D printed vein vasculature is designed and fabricated to simulate the thrombolysis of system in blood vessel. Murine tail thrombus model is also built to evaluate thrombolysis in vivo. Consequently, localized hyperthermia is validated to possess an effective enhancement for thrombolysis. Therefore, according to the results, the fabricated system demonstrates two aspects of potential superiority: controlled uPA release for reducing risk of side effects, and hyperthermia-enhanced thrombolysis locally for decreasing drug dosage. Assisted with thermal thrombolysis, the present formulated system shows a high efficiency, on-demand drug release, and thus a safer protocol for thrombolytic therapy, which fits the developing trends of precision medicine.