Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery

Erica B. Peters, Nick D. Tsihlis, Mark R. Karver, Stacey M. Chin, Bruno Musetti, Benjamin T. Ledford, Edward M. Bahnson, Samuel I Stupp, Melina R. Kibbe

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article number1801545
JournalAdvanced healthcare materials
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Amphiphiles
Atherosclerotic Plaques
Peptides
Reactive Oxygen Species
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Macrophages
Annexin A1
Nanomedicine
Nanofibers
Macrophage Activation
Nanostructures
Oxygen
Apolipoprotein A-I
Medical nanotechnology
Interferon-gamma
Lipopolysaccharides
Interferons
Atherosclerosis
Nitric Oxide

Keywords

  • Ac2-26
  • atherosclerosis
  • drug delivery
  • immunotherapy
  • nanomedicine
  • peptide amphiphile

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

Cite this

Peters, E. B., Tsihlis, N. D., Karver, M. R., Chin, S. M., Musetti, B., Ledford, B. T., ... Kibbe, M. R. (Accepted/In press). Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery. Advanced healthcare materials, [1801545]. https://doi.org/10.1002/adhm.201801545

Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery. / Peters, Erica B.; Tsihlis, Nick D.; Karver, Mark R.; Chin, Stacey M.; Musetti, Bruno; Ledford, Benjamin T.; Bahnson, Edward M.; Stupp, Samuel I; Kibbe, Melina R.

In: Advanced healthcare materials, 01.01.2019.

Research output: Contribution to journalArticle

Peters, EB, Tsihlis, ND, Karver, MR, Chin, SM, Musetti, B, Ledford, BT, Bahnson, EM, Stupp, SI & Kibbe, MR 2019, 'Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery', Advanced healthcare materials. https://doi.org/10.1002/adhm.201801545
Peters EB, Tsihlis ND, Karver MR, Chin SM, Musetti B, Ledford BT et al. Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery. Advanced healthcare materials. 2019 Jan 1. 1801545. https://doi.org/10.1002/adhm.201801545
Peters, Erica B. ; Tsihlis, Nick D. ; Karver, Mark R. ; Chin, Stacey M. ; Musetti, Bruno ; Ledford, Benjamin T. ; Bahnson, Edward M. ; Stupp, Samuel I ; Kibbe, Melina R. / Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery. In: Advanced healthcare materials. 2019.
@article{82aa746b48e246c799caca9085b51f2a,
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.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/adhm.201801545",
language = "English",
journal = "Advanced healthcare materials",
issn = "2192-2640",
publisher = "John Wiley and Sons Ltd",

}

TY - JOUR

T1 - Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery

AU - Peters, Erica B.

AU - Tsihlis, Nick D.

AU - Karver, Mark R.

AU - Chin, Stacey M.

AU - Musetti, Bruno

AU - Ledford, Benjamin T.

AU - Bahnson, Edward M.

AU - Stupp, Samuel I

AU - Kibbe, Melina R.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Ac2-26

KW - atherosclerosis

KW - drug delivery

KW - immunotherapy

KW - nanomedicine

KW - peptide amphiphile

UR - http://www.scopus.com/inward/record.url?scp=85059700031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059700031&partnerID=8YFLogxK

U2 - 10.1002/adhm.201801545

DO - 10.1002/adhm.201801545

M3 - Article

C2 - 30620448

AN - SCOPUS:85059700031

JO - Advanced healthcare materials

JF - Advanced healthcare materials

SN - 2192-2640

M1 - 1801545

ER -