Gd(III)-labeled peptide nanofibers for reporting on biomaterial localization in vivo

Adam T. Preslar, Giacomo Parigi, Mark T. McClendon, Samantha S. Sefick, Tyson J. Moyer, Chad R. Haney, Emily A. Waters, Keith W. Macrenaris, Claudio Luchinat, Samuel I Stupp, Thomas J. Meade

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Bioactive supramolecular nanostructures are of great importance in regenerative medicine and the development of novel targeted therapies. In order to use supramolecular chemistry to design such nanostructures, it is extremely important to track their fate in vivo through the use of molecular imaging strategies. Peptide amphiphiles (PAs) are known to generate a wide array of supramolecular nanostructures, and there is extensive literature on their use in areas such as tissue regeneration and therapies for disease. We report here on a series of PA molecules based on the well-established β-sheet amino acid sequence V3A3 conjugated to macrocyclic Gd(III) labels for magnetic resonance imaging (MRI). These conjugates were shown to form cylindrical supramolecular assemblies using cryogenic transmission electron microscopy and small-angle X-ray scattering. Using nuclear magnetic relaxation dispersion analysis, we observed that thermal annealing of the nanostructures led to a decrease in water exchange lifetime (τm) of hundreds of nanoseconds only for molecules that self-assemble into nanofibers of high aspect ratio. We interpret this decrease to indicate more solvent exposure to the paramagnetic moiety on annealing, resulting in faster water exchange within angstroms of the macrocycle. We hypothesize that faster water exchange in the nanofiber-forming PAs arises from the dehydration and increase in packing density on annealing. Two of the self-assembling conjugates were selected for imaging PAs after intramuscular injections of the PA C16V 3A3E3-NH2 in the tibialis anterior muscle of a murine model. Needle tracts were clearly discernible with MRI at 4 days postinjection. This work establishes Gd(III) macrocycle-conjugated peptide amphiphiles as effective tracking agents for peptide amphiphile materials in vivo over the timescale of days.

Original languageEnglish
Pages (from-to)7325-7332
Number of pages8
JournalACS Nano
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 22 2014

Fingerprint

Amphiphiles
Biocompatible Materials
Nanofibers
Biomaterials
Peptides
peptides
Nanostructures
Annealing
Magnetic resonance
Imaging techniques
annealing
magnetic resonance
Water
therapy
Supramolecular chemistry
water
Magnetic relaxation
Molecular imaging
Tissue regeneration
Molecules

Keywords

  • biomaterials
  • contrast agent
  • magnetic resonance imaging
  • nuclear magnetic relaxation dispersion
  • peptide amphiphile
  • self-assembly

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Cite this

Preslar, A. T., Parigi, G., McClendon, M. T., Sefick, S. S., Moyer, T. J., Haney, C. R., ... Meade, T. J. (2014). Gd(III)-labeled peptide nanofibers for reporting on biomaterial localization in vivo. ACS Nano, 8(7), 7325-7332. https://doi.org/10.1021/nn502393u

Gd(III)-labeled peptide nanofibers for reporting on biomaterial localization in vivo. / Preslar, Adam T.; Parigi, Giacomo; McClendon, Mark T.; Sefick, Samantha S.; Moyer, Tyson J.; Haney, Chad R.; Waters, Emily A.; Macrenaris, Keith W.; Luchinat, Claudio; Stupp, Samuel I; Meade, Thomas J.

In: ACS Nano, Vol. 8, No. 7, 22.07.2014, p. 7325-7332.

Research output: Contribution to journalArticle

Preslar, AT, Parigi, G, McClendon, MT, Sefick, SS, Moyer, TJ, Haney, CR, Waters, EA, Macrenaris, KW, Luchinat, C, Stupp, SI & Meade, TJ 2014, 'Gd(III)-labeled peptide nanofibers for reporting on biomaterial localization in vivo', ACS Nano, vol. 8, no. 7, pp. 7325-7332. https://doi.org/10.1021/nn502393u
Preslar AT, Parigi G, McClendon MT, Sefick SS, Moyer TJ, Haney CR et al. Gd(III)-labeled peptide nanofibers for reporting on biomaterial localization in vivo. ACS Nano. 2014 Jul 22;8(7):7325-7332. https://doi.org/10.1021/nn502393u
Preslar, Adam T. ; Parigi, Giacomo ; McClendon, Mark T. ; Sefick, Samantha S. ; Moyer, Tyson J. ; Haney, Chad R. ; Waters, Emily A. ; Macrenaris, Keith W. ; Luchinat, Claudio ; Stupp, Samuel I ; Meade, Thomas J. / Gd(III)-labeled peptide nanofibers for reporting on biomaterial localization in vivo. In: ACS Nano. 2014 ; Vol. 8, No. 7. pp. 7325-7332.
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