@article{a3ed94de9c9b452d8300a7c3ebc6cb21,
title = "Development of novel nanofibers targeted to smoke-injured lungs",
abstract = "Smoke inhalation injury is associated with significant mortality and current therapies remain supportive. The purpose of our study was to identify proteins upregulated in the lung after smoke inhalation injury and develop peptide amphiphile nanofibers that target these proteins. We hypothesize that nanofibers targeted to angiotensin-converting enzyme or receptor for advanced glycation end products will localize to smoke-injured lungs. Methods: Five targeting sequences were incorporated into peptide amphiphile monomers methodically to optimize nanofiber formation. Nanofiber formation was assessed by conventional transmission electron microscopy. Rats received 8 min of wood smoke. Levels of angiotensin-converting enzyme and receptor for advanced glycation end products were evaluated by immunofluorescence. Rats received the targeted nanofiber 23 h after injury via tail vein injection. Nanofiber localization was determined by fluorescence quantification. Results: Peptide amphiphile purity (>95%) and nanofiber formation were confirmed. Target proteins were increased in smoke inhalation versus sham (p < 0.001). After smoke inhalation and injection of targeted nanofibers, we found a 10-fold increase in angiotensin-converting enzyme-targeted nanofiber localization to lung (p < 0.001) versus sham with minimal localization of non-targeted nanofiber (p < 0.001). Conclusions: We synthesized, characterized, and evaluated systemically delivered targeted nanofibers that localized to the site of smoke inhalation injury in vivo. Angiotensin-converting enzyme-targeted nanofibers serve as the foundation for developing a novel nanotherapeutic that treats smoke inhalation lung injury.",
keywords = "Animal Model, Burn, Nanotechnology, Peptide amphiphile, Pulmonary",
author = "Mercel, {Alexandra I.} and Kathleen Marulanda and Gillis, {David C.} and Kui Sun and Clemons, {Tristan D.} and Smaranda Willcox and Jack Griffith and Peters, {Erica B.} and Karver, {Mark R.} and Tsihlis, {Nick D.} and Rob Maile and Stupp, {Samuel I.} and Kibbe, {Melina R.}",
note = "Funding Information: This work was supported by the National Institutes of Health (grant numbers 2T32GM008450-26 , 1R01HL116577-01 ); the American Heart Association Postdoctoral Fellowship Award (grant number 18POST33960499 ); the National Institute of General Medical Sciences of the National Institutes of Health (grant number T32GM086330 ); the Center for Regenerative Nanomedicine in the Simpson Querrey Institute at Northwestern University; the Lineberger Comprehensive Cancer Center UCRF; and an American Australian Association- Dow Chemical Company Scholarship. Funding Information: The authors would like to thank D. Hepp for assistance with manuscript submission. We acknowledge the following core facilities at UNC: the cryoEM core ( https://www.med.unc.edu/cryo-em/policies-and-procedures/ ), the Center for Structural Biology, and the Lineberger Comprehensive Cancer Center ( https://unclineberger.org ). Mark Seniw, Simpson Querrey Institute, Northwestern University, provided molecular graphics of PAs and nanofibers. The authors acknowledge the following core facilities at Northwestern University: the Peptide Synthesis Core Facility and the Analytical bioNanoTechnology Equipment Core Facility (ANTEC) of the Simpson Querrey Institute for peptide synthesis and purification. X-ray experiments were carried out at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). The authors also acknowledge the U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command , and Northwestern University for providing ongoing support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource ( NSF ECCS-2025633 ). DND-CAT is supported by E.I. DuPont de Nemours & Co., the Dow Chemical Company, and the State of Illinois. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Funding Information: This work was supported by the National Institutes of Health (grant numbers 2T32GM008450-26, 1R01HL116577-01); the American Heart Association Postdoctoral Fellowship Award (grant number 18POST33960499); the National Institute of General Medical Sciences of the National Institutes of Health (grant number T32GM086330); the Center for Regenerative Nanomedicine in the Simpson Querrey Institute at Northwestern University; the Lineberger Comprehensive Cancer Center UCRF; and an American Australian Association- Dow Chemical Company Scholarship.The authors would like to thank D. Hepp for assistance with manuscript submission. We acknowledge the following core facilities at UNC: the cryoEM core (https://www.med.unc.edu/cryo-em/policies-and-procedures/), the Center for Structural Biology, and the Lineberger Comprehensive Cancer Center (https://unclineberger.org). Mark Seniw, Simpson Querrey Institute, Northwestern University, provided molecular graphics of PAs and nanofibers. The authors acknowledge the following core facilities at Northwestern University: the Peptide Synthesis Core Facility and the Analytical bioNanoTechnology Equipment Core Facility (ANTEC) of the Simpson Querrey Institute for peptide synthesis and purification. X-ray experiments were carried out at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). The authors also acknowledge the U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University for providing ongoing support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633). DND-CAT is supported by E.I. DuPont de Nemours & Co. the Dow Chemical Company, and the State of Illinois. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = jul,
doi = "10.1016/j.biomaterials.2021.120862",
language = "English (US)",
volume = "274",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",
}