Recent Advances in Nanomedicine for Ischemic and Hemorrhagic Stroke
Recent Advances in Nanomedicine for Ischemic and Hemorrhagic Stroke
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DOI：
10.1161/strokeaha.118.022744
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发表时间：
2019-05-01
期刊：
影响因子：
8.3
通讯作者：
Vivien, Denis
中科院分区：
文献类型：
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作者：
Bonnard, Thomas;Gauberti, Maxime;Vivien, Denis
超声波也被广泛用于促进溶栓。聚焦超声的应用可以诱导血液中气泡的形成和破裂，从而导致血凝块的破裂。这种效应被称为声空化，而这种被称为声溶栓的技术已经在一系列临床试验中进行了测试，取得了一定程度的成功。23 .这种空化效应可能通过注射预先形成的气体微泡或全氟碳液滴而增强，但迄今为止，临床试验尚未证实对患者有这种益处。工程纳米技术有希望的迹象，有可能进一步提高这种方法与血栓靶向气泡或脂质体的疗效，这些气泡或脂质体在空化效应的协同作用下释放纤维蛋白溶解药物。然而，应该注意的是，作为缺血性中风治疗的实施，这种策略带来了一些挑战，如颅骨对超声的强烈衰减和出血转化的风险增加。不幸的是，在这个阶段，这些纳米溶栓方法还没有转化为患者的利益。然而，在急性缺血性脑卒中的溶栓治疗领域，问题可能不仅仅是纳米载体的固有使用，因为自1995年tPA以来，没有任何一种新的药物治疗方法在临床试验中有益。事实上，一种新的溶栓剂的临床评估在转化过程中遇到了巨大的障碍，例如与其他领域相比，需要进行大规模和昂贵的临床试验，需要将这种新疗法与tPA的标准治疗联合进行测试（如果在4.5小时的治疗窗口内进行测试），或者考虑到4.5小时时间窗口后面部损伤的不可逆性，很难提供任何益处。
Ultrasound waves have also been widely explored to enhance thrombolysis. Application of focused ultrasounds can induce the formation and the collapse of gas bubbles within the blood that causes the fragmentation of blood clots. The effect is termed acoustic cavitation and the technique called sonothrombolysis has been tested in a range of clinical trials with mitigated successes. 23 This cavitation effect may be potentiated by the injection of preformed gas microbubbles or perfluorocarbon droplets but, to date, clinical trials have not confirmed this benefit for patients. There are promising signs from engineered nanotechnologies which have the potential to further improve the efficacy of this approach with thrombus-targeted bubbles or liposomes which release a cargo of fibrinolytic drug in synergy with the cavitation effect. 24 However, it should be noted that for its implementation as ischemic stroke treatment, this strategy carries several challenges such as the strong attenuation of ultrasound by the skull and the increased risk of hemorrhagic transformation.Unfortunately, at this stage, none of these nanothrombolytic approaches has been translated for patient benefit. However, in the precise field of thrombolytic therapy for acute ischemic stroke, the problem may not be solely inherent to the use of nanocarriers, as not any single new pharmacological treatment has been beneficial in clinical trials since tPA in 1995. 25 Indeed, the clinical evaluation of a new thrombolytic agent encounters massive obstacles for translation such as the need for large and expensive clinical trials compared with other fields, the requirement to test the novel treatment in combination with standard treatment of tPA (if tested within the 4.5-hour therapeutic window), or however, the difficulty to provide any benefit considering the irreversibility of damage to face when tested after the 4.5-hour time window.