journal article·2022-05-24Open access

Peptide Amphiphile Supramolecular Nanofibers Designed to Target Abdominal Aortic Aneurysms

Benjamin T. Ledford, Adam W. Akerman, Kui Sun, David C. Gillis, Jenna M. Weiss, Johnny Vang, Smaranda Willcox, Tristan D. Clemons, Hiroaki Sai, Ruomeng Qiu, Mark R. Karver, Jack D. Griffith, Nick D. Tsihlis, Samuel I. Stupp, John S. Ikonomidis, Melina R. Kibbe

ACS Nano· Volume 16· Issue 5

Abstract

An abdominal aortic aneurysm (AAA) is a localized dilation of the aorta located in the abdomen that poses a severe risk of death when ruptured. The cause of AAA is not fully understood, but degradation of medial elastin due to elastolytic matrix metalloproteinases is a key step leading to aortic dilation. Current therapeutic interventions are limited to surgical repair to prevent catastrophic rupture. Here, we report the development of injectable supramolecular nanofibers using peptide amphiphile molecules designed to localize to AAA by targeting fragmented elastin, matrix metalloproteinase 2 (MMP-2), and membrane type 1 matrix metalloproteinase. We designed four targeting peptide sequences from X-ray crystallographic data and incorporated them into PA molecules via solid phase peptide synthesis. After coassembling targeted and diluent PAs at different molar ratios, we assessed their ability to form nanofibers using transmission electron microscopy and to localize to AAA in male and female Sprague–Dawley rats using light sheet fluorescence microscopy. We found that three formulations of the PA nanofibers were able to localize to AAA tissue, but the MMP-2 targeting PA substantially outperformed the other nanofibers. Additionally, we demonstrated that the MMP-2 targeting PA nanofibers had an optimal dose of 5 mg (∼12 mg/kg). Our results show that there was not a significant difference in targeting between male and female Sprague–Dawley rats. Given the ability of the MMP-2 targeting PA nanofiber to localize to AAA tissue, future studies will investigate potential diagnostic and targeted drug delivery applications for AAA.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Aortic aneurysm repair treatments · Infectious Aortic and Vascular Conditions · Connective tissue disorders research

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

Affiliations

Department of Surgery, University of Virginia, Charlottesville, Virginia 22903, United States

Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States

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

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

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

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States

Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22904, 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 at Chapel Hill, Chapel Hill, North Carolina 27599, United States

Funding

National Institute of Environmental Health Sciences · School of Medicine, University of North Carolina at Chapel Hill · American Australian Association · North Carolina Biotech Center · Center for Regenerative Nanomedicine, Simpson Querrey Institute for BioNanotechnology, Northwestern University

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