Protein-Engineered Fibers For Drug Encapsulation Traceable via (19)F Magnetic Resonance

[Image: see text] Theranostic materials research is experiencing rapid growth driven by the interest in integrating both therapeutic and diagnostic modalities. These materials offer the unique capability to not only provide treatment but also track the progression of a disease. However, to create an ideal theranostic biomaterial without compromising drug encapsulation, diagnostic imaging must be optimized for improved sensitivity and spatial localization. Herein, we create a protein-engineered fluorinated coiled-coil fiber, Q2(TFL), capable of improved sensitivity to (19)F magnetic resonance spectroscopy (MRS) detection. Leveraging residue-specific noncanonical amino acid incorporation of trifluoroleucine (TFL) into the coiled-coil, Q2, which self-assembles into nanofibers, we generate Q2(TFL). We demonstrate that fluorination results in a greater increase in thermostability and (19)F magnetic resonance detection compared to the nonfluorinated parent, Q2. Q2(TFL) also exhibits linear ratiometric (19)F MRS thermoresponsiveness, allowing it to act as a temperature probe. Furthermore, we explore the ability of Q2(TFL) to encapsulate the anti-inflammatory small molecule, curcumin (CCM), and its impact on the coiled-coil structure. Q2(TFL) also provides hyposignal contrast in (1)H MRI, echogenic signal with high-frequency ultrasound and sensitive detection by (19)F MRS in vivo illustrating fluorination of coiled-coils for supramolecular assembly and their use with (1)H MRI, (19)F MRS and high frequency ultrasound as multimodal theranostic agents.