Magnetically active Fe3O4 nanorods loaded with tissue plasminogen activator for enhanced thrombolysis

被引:49
作者
Hu, Jiangnan [1 ,2 ]
Huang, Weijie [3 ]
Huang, Shengwei [1 ,2 ]
ZhuGe, Qichuan [1 ]
Jin, Kunlin [1 ,2 ]
Zhao, Yiping [3 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 1, Zhejiang Prov Key Lab Aging & Neurol Disorder Res, Wenzhou 325000, Peoples R China
[2] Univ North Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA
[3] Univ Georgia, Dept Phys & Astron, Nanoscale Sci & Engn Ctr, Athens, GA 30602 USA
基金
美国国家科学基金会; 中国国家自然科学基金; 美国国家卫生研究院;
关键词
magnetic nanorods; drug delivery; enhanced thrombolysis; tissue plasminogen activator; iron oxide; ACUTE ISCHEMIC-STROKE; MEDIATED THROMBOLYSIS; NANOPARTICLES; THERAPY; MICROBUBBLES; FIBRINOLYSIS; ALTEPLASE; DISEASE; MODEL; TRIAL;
D O I
10.1007/s12274-016-1152-4
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Systemic thrombolysis with intravenous tissue plasminogen activator (tPA) remains the only proven treatment that is effective in improving the clinical outcome of patients with acute ischemic stroke. However, thrombolytic therapy has some major limitations such as hemorrhage, neurotoxicity, and the short time window for the treatment. In this study, we designed iron oxide (Fe3O4) nanorods loaded with 6% tPA, which could be released within similar to 30 min. The Fe3O4 nanorods could be targeted to blood clots under magnetic guidance. In addition, the release of tPA could be significantly increased using an external rotating magnetic field, which subsequently resulted in a great improvement in the thrombolytic efficiency. Systematic and quantitative studies revealed the fundamental physical processes involved in the enhanced thrombolysis, while the in vitro thrombolysis assay showed that the proposed strategy could improve thrombolysis and recanalization rates and reduce the risk of tPA-mediated hemorrhage in vivo. Such a strategy will be very useful for the treatment of ischemic stroke and other deadly thrombotic diseases such as myocardial infarction and pulmonary embolism in clinical settings.
引用
收藏
页码:2652 / 2661
页数:10
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