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ACS Nano. 2019 Mar 26;13(3):2969-2985. doi: 10.1021/acsnano.8b07481. Epub 2019 Feb 19.

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

Author information

1
Department of Chemical and Biomolecular Engineering , New York University Tandon School of Engineering , Brooklyn , New York 11201 , United States.
2
Center for Advanced Imaging Innovation and Research (CAI2R) , New York University School of Medicine , New York , New York 10016 , United States.
3
Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology , New York University School of Medicine , New York , New York 10016 , United States.
4
Department of Biomedical Engineering , SUNY Downstate Medical Center , Brooklyn , New York 11203 , United States.
5
Department of Chemistry , New York University , New York , New York 10012 , United States.
6
Department of Biomaterials , New York University College of Dentistry , New York , New York 10010 , United States.

Abstract

Engineered proteins provide an interesting template for designing fluorine-19 (19F) 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 19F 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 ( T2) times and unaffected spin-lattice relaxation ( T1) times. The nearly unchanging T1 relaxation rates and linearly dependent T2 relaxation rates have allowed for detection via zero echo time 19F MRI, and the in vivo MR potential has been preliminarily explored using 19F 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 19F MRI/MRS-traceable theranostic agents.

KEYWORDS:

19F MRI; drug delivery; micelle; protein engineering; self-assembly; theranostic; thermoresponsiveness

PMID:
30758189
DOI:
10.1021/acsnano.8b07481

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