TY - JOUR
T1 - Protein-Engineered Nanoscale Micelles for Dynamic 19 F Magnetic Resonance and Therapeutic Drug Delivery
AU - Hill, Lindsay K.
AU - Frezzo, Joseph A.
AU - Katyal, Priya
AU - Hoang, Dung Minh
AU - Ben Youss Gironda, Zakia
AU - Xu, Cynthia
AU - Xie, Xuan
AU - Delgado-Fukushima, Erika
AU - Wadghiri, Youssef Z.
AU - Montclare, Jin Kim
PY - 2019/3/26
Y1 - 2019/3/26
N2 - 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.
AB - 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.
KW - F MRI
KW - drug delivery
KW - micelle
KW - protein engineering
KW - self-assembly
KW - theranostic
KW - thermoresponsiveness
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U2 - 10.1021/acsnano.8b07481
DO - 10.1021/acsnano.8b07481
M3 - Article
C2 - 30758189
AN - SCOPUS:85062322479
VL - 13
SP - 2969
EP - 2985
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 3
ER -