@article{b7fb0afdd21a492ba8c8bed3575003cf,
title = "Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery",
abstract = "Nanomedicine is a promising, noninvasive approach to reduce atherosclerotic plaque burden. However, drug delivery is limited without the ability of nanocarriers to sense and respond to the diseased microenvironment. In this study, nanomaterials are developed from peptide amphiphiles (PAs) that respond to the increased levels of matrix metalloproteinases 2 and 9 (MMP2/9) or reactive oxygen species (ROS) found within the atherosclerotic niche. A pro-resolving therapeutic, Ac2-26, derived from annexin-A1 protein, is tethered to PAs using peptide linkages that cleave in response to MMP2/9 or ROS. By adjusting the molar ratios and processing conditions, the Ac2-26 PA can be co-assembled with a PA containing an apolipoprotein A1-mimetic peptide to create a targeted, therapeutic nanofiber (ApoA1-Ac226 PA). The ApoA1-Ac2-26 PAs demonstrate release of Ac2-26 within 24 h after treatment with MMP2 or ROS. The niche-responsive ApoA1-Ac2-26 PAs are cytocompatible and reduce macrophage activation from interferon gamma and lipopolysaccharide treatment, evidenced by decreased nitric oxide production. Interestingly, the linkage chemistry of ApoA1-Ac2-26 PAs significantly affects macrophage uptake and retention. Taken together, these findings demonstrate the potential of PAs to serve as an atheroma niche-responsive nanocarrier system to modulate the inflammatory microenvironment, with implications for atherosclerosis treatment.",
keywords = "Ac2-26, atherosclerosis, drug delivery, immunotherapy, nanomedicine, peptide amphiphile",
author = "Peters, {Erica B.} and Tsihlis, {Nick D.} and Karver, {Mark R.} and Chin, {Stacey M.} and Bruno Musetti and Ledford, {Benjamin T.} and Bahnson, {Edward M.} and Stupp, {Samuel I.} and Kibbe, {Melina R.}",
note = "Funding Information: This study was supported in part by funding from the National Institutes of Health (1R01HL116577-01) and the University of North Carolina{\textquoteright}s School of Medicine. E.B.P. was supported by the American Heart Association Postdoctoral Fellowship Award #18POST33960499. E.M.B. is a KL2 scholar partially supported by the UNC Clinical and Translational Science Award-K12 Scholars Program funded by the National Center for Advancing Translational Sciences, US. (KL2TR002490, 2018). B.M. was partially supported by the Uruguayan Commission for Scientific Research (CSIC) and Program for the Development of Basic Science (PEDECIBA). S.I.S. acknowledges funding from the Louis A. Simpson and Kimberly K. Querrey Center for Regenerative Nanomedicine at Northwestern University through a CRN Catalyst Award. The HPLC-MS analysis utilized equipment supported by the National Science Foundation under Grant No. CHE-1726291. The authors gratefully acknowledge Dr. Jack Griffith and Smaranda Wilcox for assistance with conventional TEM. The UNC Electron Microscopy Facility is supported in part by the Lineberger Comprehensive Cancer CenterUCRF. Peptide amphiphile synthesis was performed in the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop this facility and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205). Portions of this work were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, E.I. DuPont de Nemours & Co., and The Dow Chemical Company. 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. Data was collected using an instrument funded by the National Science Foundation under Award Number 0960140. This material is based upon work supported by the National Science Foundation under Grant No. (CHE-1726291). Funding Information: This study was supported in part by funding from the National Institutes of Health (1R01HL116577-01) and the University of North Carolina's School of Medicine. E.B.P. was supported by the American Heart Association Postdoctoral Fellowship Award #18POST33960499. E.M.B. is a KL2 scholar partially supported by the UNC Clinical and Translational Science Award-K12 Scholars Program funded by the National Center for Advancing Translational Sciences, US. (KL2TR002490, 2018). B.M. was partially supported by the Uruguayan Commission for Scientific Research (CSIC) and Program for the Development of Basic Science (PEDECIBA). S.I.S. acknowledges funding from the Louis A. Simpson and Kimberly K. Querrey Center for Regenerative Nanomedicine at Northwestern University through a CRN Catalyst Award. The HPLC-MS analysis utilized equipment supported by the National Science Foundation under Grant No. CHE-1726291. The authors gratefully acknowledge Dr. Jack Griffith and Smaranda Wilcox for assistance with conventional TEM. The UNC Electron Microscopy Facility is supported in part by the Lineberger Comprehensive Cancer CenterUCRF. Peptide amphiphile synthesis was performed in the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop this facility and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205). Portions of this work were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, E.I. DuPont de Nemours & Co., and The Dow Chemical Company. 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. Data was collected using an instrument funded by the National Science Foundation under Award Number 0960140. This material is based upon work supported by the National Science Foundation under Grant No. (CHE-1726291). Publisher Copyright: {\textcopyright} 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2019",
month = feb,
day = "7",
doi = "10.1002/adhm.201801545",
language = "English (US)",
volume = "8",
journal = "Advanced Healthcare Materials",
issn = "2192-2640",
publisher = "John Wiley and Sons Ltd",
number = "3",
}