Human hair derived uPA loaded capsules with dual near-infrared (I and II biowindows) laser responsive capabilities for multi-effective thrombolysis therapy
Human hair derived uPA loaded capsules with dual near-infrared (I and II biowindows) laser responsive capabilities for multi-effective thrombolysis therapy
复制标题
人发衍生的 uPA 负载胶囊具有双近红外（I 和 II 生物窗）激光响应能力，可实现多重有效的溶栓治疗
DOI：
10.1039/d0tb02242j
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发表时间：
2020-12-21
影响因子：
7
通讯作者：
Wang, Xiaolei
中科院分区：
文献类型：
--
作者：
Fang, Cuifu;Zhong, Zhiwei;Wang, Xiaolei
药物剂量失控导致的大出血等问题是临床溶栓治疗的主要障碍，突出的原因是有效的溶栓药物系统缺乏靶向性和控释能力。近年来，本课题组证实了光热效应可以促进尿激酶型纤溶酶原激活剂(UPA)的溶栓作用。然而，传统的光热剂价格相对较高或含有重金属。如果能够开发出毒性低、重金属元素最少、易于获得(最好是由人类自己提供)的药物传递系统，它们将在未来的相关应用中具有价值。本研究首次将uPA载人黑发衍生明胶纳米粒(uPA@HBHNP@GNCS)应用于溶栓治疗。在近红外I窗口(NIR-I)或II窗口(NIR-II)激光照射下，HBHNP的光热效应被触发，促进包裹在外层的明胶融化，从而实现uPA的靶向释放。体内外实验表明，该体系对近红外的深度响应(尤其是II窗)具有良好的溶栓效果，生物安全性较好。总之，所提出的毛发衍生药物释放系统具有来源人类、成本低、重金属成分最少、对近红外(II)窗口激光响应深、生物相容性好的特点，有望扩展到某些疾病的治疗，甚至是深部组织区域的治疗。
Problems such as massive hemorrhage caused by uncontrolled drug dosage are the main significant obstacles in clinical thrombolytic therapy, which are prominently due to the lack of targeting and controlled release ability of efficient thrombolytic drug systems. In recent years, our team demonstrated that the photothermal effect can facilitate the thrombolytic effect of urokinase plasminogen activator (uPA). However, conventional photothermal agents are relatively expensive or contain heavy metals. If drug delivery systems with low toxicity, minimized heavy metal elements and easy accessibility (preferably provided by human self) can be developed, they will be of value in the future related applications. Herein, uPA-loaded human black hair derived nanoparticles with gelatin capsules (uPA@HBHNP@GNCs) were applied for the first time as a thrombolytic system. Upon irradiation by near-infrared I window (NIR-I) laser or II window (NIR-II) laser, the photothermal effect of HBHNP was triggered to promote the melting of the gelatin encapsulated around the outer layer, thereby realizing the targeted release of uPA. The in vitro and in vivo experiments demonstrated that the deep response to NIR (especially II window) of this system exhibited a satisfactory thrombolytic effect with ideal biosafety. Briefly, the proposed hair derived drug delivery system has the characteristics of human source, low cost, minimum heavy metal components, deep response to NIR (II window) laser, and good biocompatibility, which is expected to be expanded to the treatment for some diseases, even in deep tissue areas.