Alexandra I Mercel1, Kathleen Marulanda1, David C Gillis1, Kui Sun1, Tristan D Clemons2, Smaranda Willcox3, Jack Griffith3, Erica B Peters1, Mark R Karver4, Nick D Tsihlis1, Rob Maile5, Samuel I Stupp6, Melina R Kibbe7. 1. Department of Surgery, University of North Carolina, Chapel Hill, NC, 27599, USA. 2. Simpson Querrey Institute, Northwestern University, Chicago, IL, 60611, USA; Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA. 3. Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599, USA. 4. Simpson Querrey Institute, Northwestern University, Chicago, IL, 60611, USA. 5. Department of Surgery, University of North Carolina, Chapel Hill, NC, 27599, USA; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, 27599, USA; Curriculum of Toxicology and Environmental Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA. 6. Simpson Querrey Institute, Northwestern University, Chicago, IL, 60611, USA; Department of Chemistry, Northwestern University, Evanston, IL, 60208, USA; Department of Materials Science & Engineering, Northwestern University, Evanston, IL, 60208, USA; Department of Medicine, Northwestern University, Chicago, IL, 60611, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA. 7. Department of Surgery, University of North Carolina, Chapel Hill, NC, 27599, USA; Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, 27599, USA. Electronic address: melina_kibbe@med.unc.edu.
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. Published by Elsevier Ltd.
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. Published by Elsevier Ltd.
Authors: Sameer S Kadri; Andrew C Miller; Samuel Hohmann; Stephanie Bonne; Carrie Nielsen; Carmen Wells; Courtney Gruver; Sadeq A Quraishi; Junfeng Sun; Rongman Cai; Peter E Morris; Bradley D Freeman; James H Holmes; Bruce A Cairns; Anthony F Suffredini Journal: Chest Date: 2016-06-15 Impact factor: 9.410
Authors: Yumiko Imai; Keiji Kuba; Shuan Rao; Yi Huan; Feng Guo; Bin Guan; Peng Yang; Renu Sarao; Teiji Wada; Howard Leong-Poi; Michael A Crackower; Akiyoshi Fukamizu; Chi-Chung Hui; Lutz Hein; Stefan Uhlig; Arthur S Slutsky; Chengyu Jiang; Josef M Penninger Journal: Nature Date: 2005-07-07 Impact factor: 49.962