Targeted Multifunctional Multimodal Protein-Shell Microspheres as Cancer Imaging Contrast Agents
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In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications.
A preclinical rat model was used to demonstrate the feasibility of the multimodal multifunctional microspheres as contrast agents in ultrasound, MM-OCT and MRI. Microspheres were functionalized with the RGD peptide ligand, which is targeted to αvβ3 integrin receptors that are over-expressed in tumors and atherosclerotic lesions.
These microspheres, which contain iron oxide nanoparticles in their cores, can be modulated externally using a magnetic field to create dynamic contrast in MM-OCT. With the presence of iron oxide nanoparticles, these agents also show significant negative T2 contrast in MRI. Using ultrasound B-mode imaging at a frequency of 30 MHz, a marked enhancement of scatter intensity from in vivo rat mammary tumor tissue was observed for these targeted protein microspheres.
Preliminary results demonstrate multimodal contrast-enhanced imaging of these functionalized microsphere agents with MRI, MM-OCT, ultrasound imaging, and fluorescence microscopy, including in vivo tracking of the dynamics of these microspheres in real-time using a high-frequency ultrasound imaging system. These targeted oil-filled protein microspheres with the capacity for high drug-delivery loads offer the potential for local delivery of lipophilic drugs under image guidance.
Key wordsMagnetomotive optical coherence tomography Ultrasound imaging Magnetic resonance imaging Contrast agents Protein microspheres Iron oxide RGD peptide Alpha(v) beta(3) targeting
This research was supported in part by grants from the National Institutes of Health (Roadmap Initiative, NIBIB R21 EB005321, NIBIB R01 EB009073, and NCI RC1 CA147096).
Conflicts of Interest
Stephen A. Boppart receives royalties related to optical coherence tomography for patents licensed by the Massachusetts Institute of Technology. He is also co-founder of Diagnostic Photonics, Inc., a company developing Interferometric Synthetic Aperture Microscopy for medical applications, and he receives funding for sponsored research projects from Welch Allyn, Inc. and Samsung, Inc., related to optical imaging technologies. All other authors report no real or perceived conflicts of interest.
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