Protein-Engineered Nanoscale Micelles for Dynamic ¹⁹ F 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 "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.