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

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 “fluor...

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Bibliographic Details
Published inACS nano Vol. 13; no. 3; pp. 2969 - 2985
Main Authors Hill, Lindsay K, Frezzo, Joseph A, Katyal, Priya, Hoang, Dung Minh, Ben Youss Gironda, Zakia, Xu, Cynthia, Xie, Xuan, Delgado-Fukushima, Erika, Wadghiri, Youssef Z, Montclare, Jin Kim
Format Journal Article
LanguageEnglish
Published American Chemical Society 26.03.2019
Subjects
micelle
self-assembly
protein engineering
drug delivery
theranostic
19F MRI
thermoresponsiveness
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Summary: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 (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 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.
Bibliography:L. K. Hill and J. A. Frezzo contributed equally to this work.
Author Contributions
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.8b07481