DataVXACS NanoPaper
journal article·2020-06-23Open access

Development of Optimized Tissue-Factor-Targeted Peptide Amphiphile Nanofibers to Slow Noncompressible Torso Hemorrhage

Mia K. Klein, Hussein Aziz Kassam, Robert H. Lee, Wolfgang Bergmeier, Erica B. Peters, David C. Gillis, Brooke R. Dandurand, Jessica R. Rouan, Mark R. Karver, Mark D. Struble, Tristan D. Clemons, Liam C. Palmer, Brian Gavitt, Timothy A. Pritts, Nick D. Tsihlis, Samuel I. Stupp, Melina R. Kibbe

ACS Nano· Volume 14· Issue 6
Publisher pageOpen full text
Source abstract

Abstract

Noncompressible torso hemorrhage accounts for a significant portion of preventable trauma deaths. We report here on the development of injectable, targeted supramolecular nanotherapeutics based on peptide amphiphile (PA) molecules that are designed to target tissue factor (TF) and, therefore, selectively localize to sites of injury to slow hemorrhage. Eight TF-targeting sequences were identified, synthesized into PA molecules, coassembled with nontargeted backbone PA at various weight percentages, and characterized via circular dichroism spectroscopy, transmission electron microscopy, and X-ray scattering. Following intravenous injection in a rat liver hemorrhage model, two of these PA nanofiber coassemblies exhibited the most specific localization to the site of injury compared to controls (p < 0.05), as quantified using immunofluorescence imaging of injured liver and uninjured organs. To determine if the nanofibers were targeting TF in vivo, a mouse saphenous vein laser injury model was performed and showed that TF-targeted nanofibers colocalized with fibrin, demonstrating increased levels of nanofiber at TF-rich sites. Thromboelastograms obtained using samples of heparinized rat whole blood containing TF demonstrated that no clots were formed in the absence of TF-targeted nanofibers. Lastly, both PA nanofiber coassemblies decreased blood loss in comparison to sham and backbone nanofiber controls by 35–59% (p < 0.05). These data demonstrate an optimal TF-targeted nanofiber that localizes selectively to sites of injury and TF exposure, and, interestingly, reduces blood loss. This research represents a promising initial phase in the development of a TF-targeted injectable therapeutic to reduce preventable deaths from hemorrhage.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Hemoglobin structure and function · Trauma, Hemostasis, Coagulopathy, Resuscitation · Neuropeptides and Animal Physiology

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Surgery and Center for Nanotechnology in Drug Delivery, University of North Carolina, Chapel Hill, North Carolina 27599, United States

Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, United States

UNC Blood Research Center, University of North Carolina, Chapel Hill, North Carolina 27514, United States

Simpson Querrey Institute, Northwestern University, Chicago, Illinois 60611, United States

Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States

School of Molecular Sciences, University of Western Australia, Perth, WA 6009, Australia

United States Air Force School of Aerospace Medicine, Wright-Patterson AFB, Ohio 45433, United States

Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267, United States

Department of Materials Science and Engineering, Northwestern University,, Evanston, Illinois 60208, United States

Department of Medicine, Northwestern University, Chicago, Illinois 60611, United States

Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, United States

Department of Biomedical Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, United States

Funding

School of Medicine, University of North Carolina at Chapel Hill · National Heart, Lung, and Blood Institute · American Heart Association · U.S. Department of Defense · American Australian Association · Division of Materials Research · International Institute for Nanotechnology, Northwestern University · Center for Regenerative Nanomedicine, Northwestern University · State of Illinois

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