title: Self-propelled particles that transport cargo through flowing blood and halt hemorrhage.
abstract: 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 loaded with active thrombin, these particles worked effectively as a hemostatic agent and halted severe hemorrhage in multiple animal models 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 self-fueled transport of particles can function in vivo to enhance drug delivery.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. ; Biomedical Engineering Program, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: James R
authors.initials: JR
authors.lastname: Baylis
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. ; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Ju Hun
authors.initials: JH
authors.lastname: Yeon
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. ; Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Max H
authors.initials: MH
authors.lastname: Thomson
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. ; Biomedical Engineering Program, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Amir
authors.initials: A
authors.lastname: Kazerooni
authors.affiliation: Division of Emergency Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Emergency Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Alex E
authors.initials: AE
authors.lastname: St John
authors.affiliation: Division of Emergency Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Esther B
authors.initials: EB
authors.lastname: Lim
authors.affiliation: Division of Emergency Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Chien
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Anna
authors.initials: A
authors.lastname: Lee
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Jesse Q
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. ; Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: James M
authors.initials: JM
authors.lastname: Piret
authors.affiliation: Department of Radiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Machan
authors.affiliation: Division of Global Health and Human Rights, Department of Emergency Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Burke
authors.affiliation: Division of Emergency Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: White
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. ; Biomedical Engineering Program, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. ; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Kastrup
keywords: Antifibrinolytic; Bubble propulsion; Calcium carbonate; Coagulation; Foaming; Hemostasis; Micromotors; Self-propelling particles; Surgery; drug delivery