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

摘要

Engineered proteins provide an interesting template for designing fluorine-19 (F-19) 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 F-19 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 F-19 MRI, and the in vivo MR potential has been preliminarily explored using F-19 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 F-19 MRI/MRS-traceable theranostic agents.