Fluorinated Nanoparticles: A Novel Technology Platform for Multimodal Biomedical Imaging Applications

Abstract

Fluorinated compounds have many applications in medicine, including oxygen transport, drug delivery vehicles, and contrast agents in medicine due to fluorine's unique chemical and nuclear properties. Fluorinated compounds have been used in microbubble contrast agents for ultrasound imaging, positron sources for PET imaging, and as an imaging probe in 19F MRI. Additionally, fluorinated organic compounds generate a high ionization yield of fluorine in secondary ion mass spectrometry (SIMS), which is gaining recognition as an in vitro cellular imaging technique. This suggests that fluorinated SIMS "chromophores" could be developed for diagnostic imaging that target specific cell markers. The goal of this work has been to develop a fluorinated nanoparticle platform technology that could be used for multiple biomedical imaging techniques, including in vivo and in vitro diagnostic imaging. Fluorinated nanoparticles were synthesized from one of two fluorinated monomers, as well as a hydrophilic monomer and hydrophilic crosslinker to enhance the aqueous colloidal stability of the nanoparticles. Nanoparticles were then characterized to determine their chemical properties, colloidal stability, and suitability for use as a 19F MRI and SIMS contrast agent. Particle sizes were measured using small angle neutron scattering and dynamic light scattering, nuclear magnetic resonance signal was measured using 19F NMR, and chemical functional groups were determined using FTIR. Particle size and structure were also examined using scanning electron microscopy and transmission electron microscopy. The results suggested that nanoparticles are colloidally stable, exhibit a strong 19F NMR signal and a high fluorinated ion yield in SIMS, and contain functional groups that would facilitate conjugation with antibodies or other ligands for targeted nanoparticle delivery to pathological tissues of interest for imaging. Nanoparticles were also developed for bimodal optical fluorescence imaging and SIMS imaging by incorporating a fluorescent functionality within the particles. The fluorescent-fluorinated nanoparticles were conjugated with LABL peptide, which binds to ICAM-1 on the surface of endothelial cells to facilitate T-cell recruitment to sites of inflammation. In vitro cell uptake studies show enhanced binding and uptake of LABL-conjugated fluorescent-fluorinated nanoparticles compared to non-conjugated nanoparticles, suggesting that this technique could be used as a targeting mechanism for cellular imaging. A cell preparation method was also designed for SIMS imaging, which showed great cellular detail. Current work is examining the suitability of fluorinated-fluorescent nanoparticles as SIMS imaging probes for diagnostic imaging using the cell preparation method designed for this work.