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

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 “ f luorinated t hermo r esponsive a ssembled p rotein” (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.