Protein-Engineered Fibers For Drug Encapsulation Traceable via 19 F 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 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.
Competing Interests: The authors declare no competing financial interest.
(© 2023 The Authors. Published by American Chemical Society.)