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基于血细胞膜伪装的内在生物趋化解决方案可实现富勒醇溶栓

Intrinsic Biotaxi Solution Based on Blood Cell Membrane Cloaking Enables Fullerenol Thrombolysis .

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterial & Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, 19B YuquanLu, Shijingshan District, Beijing 100049, China.

University of Chinese Academy of Sciences, 19A YuquanLu, Shijingshan District, Beijing 100049, China.

出版信息

ACS Appl Mater Interfaces. 2020 Apr 1;12(13):14958-14970. doi: 10.1021/acsami.0c01768. Epub 2020 Mar 17.

Abstract

We report the construction of blood cell membrane cloaked mesoporous silica nanoparticles for delivery of nanoparticles [fullerenols (Fols)] with fibrinolysis activity which endows the active Fol with successful thrombolysis effect . , Fols present excellent fibrinolysis activity, and the Fol with the best fibrinolysis activity is screened based on the correlation between Fols' structure and their fibrinolysis activity. However, the thrombolytic effect is not satisfactory. To rectify the unsatisfactory situation and avoid the exogenous stimuli, a natural blood cell membrane cloaking strategy with loading the active Fol is chosen to explore as a novel thrombolysis drug. After cloaking, the therapeutic platform prolongs blood circulation time and enhances the targeting effect. Interestingly, compared with platelet membrane cloaking, red blood cell (RBC) membrane cloaking demonstrates stronger affinity with fibrin and more enrichment at the thrombus site. The Fol with RBC cloaking shows quick and efficient thrombolysis efficacy with less bleeding risk, more excellent blood compatibility, and better biosafety when compared with the clinical drug urokinase (UK). These findings not only validate the blood cell membrane cloaking strategy as an effective platform for Fol delivery on thrombolysis treatment, but also hold a great promising solution for other active nanoparticle deliveries .

摘要

我们构建了一种血细胞膜包裹的介孔硅纳米粒子,用于递送具有纤溶活性的纳米颗粒[富勒醇(Fols)],这赋予了活性 Fol 成功的溶栓效果。Fols 表现出优异的纤溶活性,并且根据 Fols 的结构与其纤溶活性之间的相关性筛选出具有最佳纤溶活性的 Fol。然而,溶栓效果并不理想。为了纠正这种不理想的情况并避免外源刺激,选择了一种天然的血细胞膜包裹策略来负载活性 Fol,以探索其作为新型溶栓药物的应用。包裹后,治疗平台延长了血液循环时间并增强了靶向效果。有趣的是,与血小板膜包裹相比,红细胞(RBC)膜包裹与纤维蛋白具有更强的亲和力,并在血栓部位更富集。与临床药物尿激酶(UK)相比,具有 RBC 包裹的 Fol 表现出更快、更有效的溶栓效果,出血风险更小,血液相容性更好,生物安全性更好。这些发现不仅验证了血细胞膜包裹策略作为 Fol 递送至溶栓治疗的有效平台,而且为其他活性纳米颗粒递释提供了有前途的解决方案。

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