zSelf-propelled particles that transport cargo through flowing blood and halt hemorrhage

被引:180
作者
Baylis, James R. [1 ,2 ]
Yeon, Ju Hun [1 ,3 ]
Thomson, Max H. [1 ,4 ]
Kazerooni, Amir [1 ,2 ]
Wang, Xu [5 ]
St John, Alex E. [5 ]
Lim, Esther B. [5 ]
Chien, Diana [5 ]
Lee, Anna [1 ]
Zhang, Jesse Q. [1 ]
Piret, James M. [1 ,6 ]
Machan, Lindsay S. [4 ]
Burke, Thomas F. [7 ,8 ]
White, Nathan J. [5 ]
Kastrup, Christian J. [1 ,2 ,3 ]
机构
[1] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
[2] Univ British Columbia, Biomed Engn Program, Vancouver, BC V6T 1Z4, Canada
[3] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z4, Canada
[4] Univ British Columbia, Dept Radiol, Fac Med, Vancouver, BC V6T 1Z4, Canada
[5] Univ Washington, Div Emergency Med, Seattle, WA 98195 USA
[6] Univ British Columbia, Dept Chem & Biol Engn, Vancouver, BC V6T 1Z4, Canada
[7] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Boston, MA 02114 USA
[8] Harvard Med Sch, Boston, MA 02114 USA
来源
SCIENCE ADVANCES | 2015年 / 1卷 / 09期
基金
加拿大健康研究院;
关键词
AUTONOMOUS MOVEMENT; MICROMOTORS; DELIVERY; DEATH; MODEL;
D O I
10.1126/sciadv.1500379
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Delivering therapeutics deep into damaged tissue during bleeding is challenging because of the outward flow of blood. When coagulants cannot reach and clot blood at its source, uncontrolled bleeding can occur and increase surgical complications and fatalities. Self-propelling particles have been proposed as a strategy for transporting agents upstream through blood. Many nanoparticle and microparticle systems exhibiting autonomous or collective movement have been developed, but propulsion has not been used successfully in blood or used in vivo to transport therapeutics. We show that simple gas-generating microparticles consisting of carbonate and tranexamic acid traveled through aqueous solutions at velocities of up to 1.5 cm/s and delivered therapeutics millimeters into the vasculature of wounds. The particles transported themselves through a combination of lateral propulsion, buoyant rise, and convection. When loadedwith active thrombin, these particles worked effectively as a hemostatic agent and halted severe hemorrhage inmultiple animalmodels of intraoperative and traumatic bleeding. Many medical applications have been suggested for self-propelling particles, and the findings of this study show that the active selffueled transport of particles can function in vivo to enhance drug delivery.
引用
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页数:8
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