Engineered protein–iron oxide hybrid biomaterial for MRI-traceable drug encapsulation

Abstract

Labeled protein-based scaffolds have become a popular biomaterial for tissue-engineered implants. Labeling of protein biomaterials, including with ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticles, has enabled a wide variety of imaging...

Supramolecular Assembly and Small-Molecule Binding by Protein-Engineered Coiled-Coil Fibers

“…19 Docking was performed in Rosetta using the GALigand Docking protocol in virtual high-screening mode (VSH) 20 to allow sampling of both the receptor and ligand conformational space. To accommodate the N-and C-terminal possible sites of the long and narrow cavity of the protein coiled coil, 21 CCM was docked with starting positions inside the first N-terminal half of the coiled coil and in the second C-terminal half of the coiled coil. One hundred models were generated from each starting conformation for a total of two hundred models, the best of which was used for analysis.…”

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

“…Coiled-coil proteins have traditionally been studied for their hydrophobic small molecule-binding ability due to the presence of a hydrophobic pore. ,,, In particular, curcumin (CCM) , has been used as a model candidate drug due to its therapeutic use as an antiproliferative, antibacterial, and anti-inflammatory agent. − We assess the ability of Q2 TFL to bind CCM (Figure b) and the impact of encapsulation on Q2 TFL structure and stability, where Q2 TFL exhibits a K d of 0.06 μM/μM [CCM:protein] (0.03–0.09 μM/μM @ 95% CI), which translates to an 8:1 ratio of monomer to CCM, a significant increase compared to Q2. We use 2 K d or a ratio of 0.12 to mark saturation of CCM binding and where a negligible increase in fluorescence is seen .…”

“…31 Conversely, we have also shown the ability to use protein fibers for theranostic imaging by biorthogonal azide−alkyne cycloaddition of a designed coiled-coil protein with azidohomoalanine (AHA), Q AHA , to an alkyne-bearing iron oxide templating peptide, CMms6. 32 The hybrid Q AHA -X-CMms6 bearing the templated ultrasmall superparamagnetic iron oxide (USPIO) biomaterial is capable of doxorubicin encapsulation and exhibits sensitive T 2 *-weighted MRI darkening in part due to the multitude of USPIOs spaced along a single protein fiber assembly. 32 The Q AHA also establishes our fibers to be capable of concentrated and sustained release.…”

“… 32 The hybrid Q AHA -X-CMms6 bearing the templated ultrasmall superparamagnetic iron oxide (USPIO) biomaterial is capable of doxorubicin encapsulation and exhibits sensitive T 2 *- weighted MRI darkening in part due to the multitude of USPIOs spaced along a single protein fiber assembly. 32 The Q AHA also establishes our fibers to be capable of concentrated and sustained release. 32 While Q highlights the benefits of using a self-assembling fiber to confine many MR-sensitive USPIOs and provides unique T 2 *-darkening, it suffers from the addition of several postpurification synthesis steps.…”

Coiled-Coil Protein Hydrogels Engineered with Minimized Fiber Diameters for Sustained Release of Doxorubicin in Triple-Negative Breast Cancer

“…It becomes increasingly important to provide increased delivery or targeting of chemotherapy in consideration of cancer chemoresistance, which is a leading cause for cancer recurrence . To overcome these issues, various biocompatible materials , like lipids, , polymers, − and proteins − have been developed as drug delivery carriers to encapsulate a chemotherapeutic and enhance its circulation and selective delivery. These materials often take the form of nanoparticles or hydrogel-based systems.…”