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

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 ¹⁹F 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 ¹⁹F magnetic resonance detection compared to the nonfluorinated parent, Q2. Q2_TFL also exhibits linear ratiometric ¹⁹F 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 ¹H MRI, echogenic signal with high-frequency ultrasound and sensitive detection by ¹⁹F MRS in vivo illustrating fluorination of coiled-coils for supramolecular assembly and their use with ¹H MRI, ¹⁹F MRS and high frequency ultrasound as multimodal theranostic agents.