Protein-Engineered Nanoscale Micelles for Dynamic 19 F Magnetic Resonance and Therapeutic Drug Delivery

Lindsay K. Hill, Joseph A. Frezzo, Priya Katyal, Dung Minh Hoang, Zakia Ben Youss Gironda, Cynthia Xu, Xuan Xie, Erika Delgado-Fukushima, Youssef Z. Wadghiri, Jin Kim Montclare

Research output: Contribution to journalArticle

Abstract

Engineered proteins provide an interesting template for designing fluorine-19 ( 19 F) magnetic resonance imaging (MRI) contrast agents, yet progress has been hindered by the unpredictable relaxation properties of fluorine. Herein, we present the biosynthesis of a protein block copolymer, termed "fluorinated thermoresponsive assembled protein" (F-TRAP), which assembles into a monodisperse nanoscale micelle with interesting 19 F NMR properties and the ability to encapsulate and release small therapeutic molecules, imparting potential as a diagnostic and therapeutic (theranostic) agent. The assembly of the F-TRAP micelle, composed of a coiled-coil pentamer corona and a hydrophobic, thermoresponsive elastin-like polypeptide core, results in a drastic depression in spin-spin relaxation (T 2 ) times and unaffected spin-lattice relaxation (T 1 ) times. The nearly unchanging T 1 relaxation rates and linearly dependent T 2 relaxation rates have allowed for detection via zero echo time 19 F MRI, and the in vivo MR potential has been preliminarily explored using 19 F magnetic resonance spectroscopy (MRS). This fluorinated micelle has also demonstrated the ability to encapsulate the small-molecule chemotherapeutic doxorubicin and release its cargo in a thermoresponsive manner owing to its inherent stimuli-responsive properties, presenting an interesting avenue for the development of thermoresponsive 19 F MRI/MRS-traceable theranostic agents.

Original languageEnglish (US)
Pages (from-to)2969-2985
Number of pages17
JournalACS nano
Volume13
Issue number3
DOIs
StatePublished - Mar 26 2019

Keywords

  • F MRI
  • drug delivery
  • micelle
  • protein engineering
  • self-assembly
  • theranostic
  • thermoresponsiveness

ASJC Scopus subject areas

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

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  • Cite this

    Hill, L. K., Frezzo, J. A., Katyal, P., Hoang, D. M., Ben Youss Gironda, Z., Xu, C., Xie, X., Delgado-Fukushima, E., Wadghiri, Y. Z., & Montclare, J. K. (2019). Protein-Engineered Nanoscale Micelles for Dynamic 19 F Magnetic Resonance and Therapeutic Drug Delivery ACS nano, 13(3), 2969-2985. https://doi.org/10.1021/acsnano.8b07481