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

doi:10.1021/acsnano.8b07481

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

Chemical and Biomolecular Engineering

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Pages (from-to)	2969-2985
Number of pages	17
Journal	ACS nano
Volume	13
Issue number	3
DOIs	https://doi.org/10.1021/acsnano.8b07481
State	Published - 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)

Access to Document

10.1021/acsnano.8b07481

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

Protein-Engineered Nanoscale Micelles for Dynamic ¹⁹ F Magnetic Resonance and Therapeutic Drug Delivery . / Hill, Lindsay K.; Frezzo, Joseph A.; Katyal, Priya et al.

In: ACS nano, Vol. 13, No. 3, 26.03.2019, p. 2969-2985.

Research output: Contribution to journal › Article › peer-review

Hill, LK, Frezzo, JA, Katyal, P, Hoang, DM, Ben Youss Gironda, Z, Xu, C, Xie, X, Delgado-Fukushima, E, Wadghiri, YZ & Montclare, JK 2019, ' Protein-Engineered Nanoscale Micelles for Dynamic ¹⁹ F Magnetic Resonance and Therapeutic Drug Delivery ', ACS nano, vol. 13, no. 3, pp. 2969-2985. https://doi.org/10.1021/acsnano.8b07481

@article{fca513fe2c9b47efb9ca45100382ec30,

title = " Protein-Engineered Nanoscale Micelles for Dynamic 19 F Magnetic Resonance and Therapeutic Drug Delivery ",

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.",

keywords = "F MRI, drug delivery, micelle, protein engineering, self-assembly, theranostic, thermoresponsiveness",

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

note = "Funding Information: This work was supported by the NSF-MRSEC Program under Award Number DMR 1420073, NSF-DMREF under Award Number DMR 1728858, the NYU Shiffrin-Myers Breast Cancer Discovery Fund, and the NYU CTSA grant UL1 TR000038 from the National Center for Advancing Translational Sciences, National Institutes of Health. Some of the experiments were performed at the NYU Langone Health Preclinical Imaging Laboratory, a shared resource partially supported by the NIH/SIG 1S10OD018337-01, the Laura and Isaac Perlmutter Cancer Center Support Grant NIH/NCI 5P30CA016087, and the NIBIB Biomedical Technology Resource Center Grant NIH P41 EB017183. The authors thank J. Schulze at the Molecular Structure Facility at UC Davis for assistance in AAA, C. Lin for his guidance with 19F NMR and subsequent analysis, J. Baquero Buitrago for supplying us with the MCF-7 xenograft CrTac:NCr-Foxn1nu mice, and O. Aristiza{\'b} al for his assistance with ultrasound-guided intratumoral injection and training on the Bruker In Vivo Xtreme II. Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

year = "2019",

month = mar,

day = "26",

doi = "10.1021/acsnano.8b07481",

language = "English (US)",

volume = "13",

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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

N1 - Funding Information: This work was supported by the NSF-MRSEC Program under Award Number DMR 1420073, NSF-DMREF under Award Number DMR 1728858, the NYU Shiffrin-Myers Breast Cancer Discovery Fund, and the NYU CTSA grant UL1 TR000038 from the National Center for Advancing Translational Sciences, National Institutes of Health. Some of the experiments were performed at the NYU Langone Health Preclinical Imaging Laboratory, a shared resource partially supported by the NIH/SIG 1S10OD018337-01, the Laura and Isaac Perlmutter Cancer Center Support Grant NIH/NCI 5P30CA016087, and the NIBIB Biomedical Technology Resource Center Grant NIH P41 EB017183. The authors thank J. Schulze at the Molecular Structure Facility at UC Davis for assistance in AAA, C. Lin for his guidance with 19F NMR and subsequent analysis, J. Baquero Buitrago for supplying us with the MCF-7 xenograft CrTac:NCr-Foxn1nu mice, and O. Aristizab́ al for his assistance with ultrasound-guided intratumoral injection and training on the Bruker In Vivo Xtreme II. Publisher Copyright: © 2019 American Chemical Society.

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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