Peptide Amphiphile Supramolecular Nanostructures as a Targeted Therapy for Atherosclerosis

Neel A. Mansukhani, Erica B. Peters, Miranda M. So, Mazen S. Albaghdadi, Zheng Wang, Mark R. Karver, Tristan D. Clemons, Jeffrey P. Laux, Nick D. Tsihlis, Samuel I Stupp, Melina R. Kibbe

Research output: Contribution to journalArticle

Abstract

The rising prevalence of cardiovascular disease worldwide necessitates novel therapeutic approaches to manage atherosclerosis. Intravenously administered nanostructures are a promising noninvasive approach to deliver therapeutics that reduce plaque burden. The drug liver X receptor agonist GW3965 (LXR) can reduce atherosclerosis by promoting cholesterol efflux from plaque but causes liver toxicity when administered systemically at effective doses, thus preventing its clinical use. The ability of peptide amphiphile nanofibers containing apolipoprotein A1–derived targeting peptide 4F to serve as nanocarriers for LXR delivery (ApoA1-LXR PA) in vivo is investigated here. These nanostructures are found to successfully target atherosclerotic lesions in a mouse model within 24 h of injection. After 8 weeks of intravenous administration, the nanostructures significantly reduce plaque burden in both male and female mice to a similar extent as LXR alone in comparison to saline-treated controls. Furthermore, they do not cause increased liver toxicity in comparison to LXR treatments, which may be related to more controlled release by the nanostructure. These findings demonstrate the potential of supramolecular nanostructures as safe, effective drug nanocarriers to manage atherosclerosis.

Original languageEnglish
Article number1900066
JournalMacromolecular Bioscience
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Amphiphiles
Nanostructures
Peptides
Atherosclerosis
Liver
Toxicity
Nanofibers
Therapeutics
Apolipoproteins
Cholesterol
Pharmaceutical Preparations
Intravenous Administration
Cardiovascular Diseases
Injections

Keywords

  • apolipoprotein A1
  • atherosclerosis
  • nanomedicine
  • peptide amphiphiles
  • supramolecular nanofibers

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Mansukhani, N. A., Peters, E. B., So, M. M., Albaghdadi, M. S., Wang, Z., Karver, M. R., ... Kibbe, M. R. (2019). Peptide Amphiphile Supramolecular Nanostructures as a Targeted Therapy for Atherosclerosis. Macromolecular Bioscience, [1900066]. https://doi.org/10.1002/mabi.201900066

Peptide Amphiphile Supramolecular Nanostructures as a Targeted Therapy for Atherosclerosis. / Mansukhani, Neel A.; Peters, Erica B.; So, Miranda M.; Albaghdadi, Mazen S.; Wang, Zheng; Karver, Mark R.; Clemons, Tristan D.; Laux, Jeffrey P.; Tsihlis, Nick D.; Stupp, Samuel I; Kibbe, Melina R.

In: Macromolecular Bioscience, 01.01.2019.

Research output: Contribution to journalArticle

Mansukhani, NA, Peters, EB, So, MM, Albaghdadi, MS, Wang, Z, Karver, MR, Clemons, TD, Laux, JP, Tsihlis, ND, Stupp, SI & Kibbe, MR 2019, 'Peptide Amphiphile Supramolecular Nanostructures as a Targeted Therapy for Atherosclerosis', Macromolecular Bioscience. https://doi.org/10.1002/mabi.201900066
Mansukhani, Neel A. ; Peters, Erica B. ; So, Miranda M. ; Albaghdadi, Mazen S. ; Wang, Zheng ; Karver, Mark R. ; Clemons, Tristan D. ; Laux, Jeffrey P. ; Tsihlis, Nick D. ; Stupp, Samuel I ; Kibbe, Melina R. / Peptide Amphiphile Supramolecular Nanostructures as a Targeted Therapy for Atherosclerosis. In: Macromolecular Bioscience. 2019.
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