Magnetic protein microspheres as dynamic contrast agents for magnetomotive optical coherence tomography

Abstract

Optical coherence tomography (OCT) is an emerging biomedical imaging modality that has been developed over the last 15 years. More recently, OCT has been used for the intraoperative imaging of tumor margins in breast cancer and axillary lymph nodes providing a real time in-vivo assessment of the tissue morphology. Traditional OCT images are limited by only being able to observe morphological structures. As diagnostic medicine continues to push for earlier detection, one must develop functional imaging modalities that would detect molecular information in-vivo allowing a real-time microscopic analysis of the tissue specimen. A novel modality of OCT called magnetomotive-OCT (MM-OCT) has been developed by our group, employing an induced modulated magnetic field with a magnetic contrast agent to create the added contrast to structural OCT images. Modified protein microspheres with a BSA protein shell functionalized with RGD peptide sequences for targeting and an oil core have been designed and synthesized. Magnetic nanoparticles (Fe 3 O 4) and Nile Red dye have been encapsulated into its oil core. These microspheres have previously been demonstrated to target cancer cells by functionalizing them with a layer of RGD peptides and could be functionalized with monoclonal antibodies. Preliminary results show that these magnetic microspheres, which are 2.0-5.0 microns in size, are readily detectable under MM-OCT when embedded in a 5% agarose gel, in a 3-D scaffold of macrophage cells previously incubated with the microspheres, and when injected in-vivo into a tumor from an NMUcarcinogen rat animal model for breast cancer.

Magnetic and Plasmonic Contrast Agents in Optical Coherence Tomography

“…Superparamagnetic iron oxides (SPIOs) are typically desired because they maintain strong magnetic susceptibility while lacking remanent magnetization. Thus, MMOCT contrast agents tend to have MIO cores between ~10-50nm, although larger particle clusters [27] or novel ferrofluid-filled microspheres [28] have been developed for certain applications.…”

Factors influencing magnetic protein nanospheres prepared by sonochemical method

“…Magnetic protein microspheres have a wide range of biomedical applications, such as optical coherence tomography, fluoroimmunoassay, cell separation, and targeted drug delivery 1–4. Magnetic protein microspheres are considered as promising materials for biomedical application, due to their biocompatibility, nontoxicity, high stability, and magnetic responsivity 5.…”

Magnetic Field-Modulated Plasmonic Scattering of Hybrid Nanorods for FFT-Weighted OCT Imaging in NIR-II

“…While the ability of OCT to generate cross-sectional images without contrast agents is often regarded as a primary strength of the technique, there are occasions where identification of select regions through a contrast agent is desired. Active contrast agents have thus been introduced to enhance image quality, , which can change their properties in response to external stimuli, such as heat, light, and magnetic field. − Magnetomotive OCT, for example, takes advantage of the dynamic responses of magnetic particles to magnetic fields for imaging contrast . The lateral displacement of magnetic particles or rotation of anisotropic magnetic nanostructures under applied magnetic fields induces stresses within the viscoelastic biological medium, creating locoregional scattering changes for imaging contrast. , Suppression of noncontrast agent background can be achieved by pixel subtraction between actively modulated OCT images. , The use of magnetic particles also enables multimodal imaging, such as magnetic resonance imaging (MRI) and magnetic particle imaging, and synergistic cancer treatment by magnetothermal therapy. − However, magnetomotive OCT is facing a few challenges during its development.…”

“…9−11 While the ability of OCT to generate cross-sectional images without contrast agents is often regarded as a primary strength of the technique, there are occasions where identification of select regions through a contrast agent is desired. Active contrast agents have thus been introduced to enhance image quality, 12,13 which can change their properties in response to external stimuli, such as heat, light, and magnetic field. 14−18 Magnetomotive OCT, for example, takes advantage of the dynamic responses of magnetic particles to magnetic fields for imaging contrast.…”