Modular Nanoparticle Probes for Personalized in Vitro and in Vivo Imaging of Cancer Cell Populations

摘要

Contrast-enhanced computed tomography (CT) and spectral (color) X-ray CT have the potential to enable molecular imaging in CT and complement PET scans and MRI scans as a cheaper yet highly sensitive, high resolution, diagnostic tool. However, there is a lack of contrast agents designed to leverage the capabilities of spectral CT fully. In this talk, we will present a modular approach we have developed to create a spectral library of core-shell nanoparticle (NPs) contrast agents. The synthesis method will have broad applications in biomedical imaging due to potential for scalable synthesis of multi-modal imaging probes (e.g., fluorescence, MRI, X-ray, plasmomc resonance), dosed delivery of therapeutics and active targeting through molecular surface functionalization. Gold NPs (Au NPs), gadolinium oxide NPs (Gd203 NPs) and hafnium oxide NPs (HfO2 NPs) core compositions were prepared at a standard size (~10 nm) using solution phase synthesis. Controlled addition of silica shells (1-15 nm) enabled controlled loading of fluorescent molecules and provided a common platform for molecular surface functionalization. Antibodies and other small molecules were efficiently conjugated to the nanoparticles using appropriate CLICK chemistry. The bioactivity and orientation of antibodies conjugated to NPs were confirmed through agglomeration assays and electron microscopy. Quantitative assays reported a steady conjugation efficiency of 75%-80%. Bioconjugation allowed the multi-modal bioactive NPs were then successfully targeted in vitro and in vivo to metastasis-promoting cdl33(+) SKOV3-IP cells, which are responsible for poor prognosis in ovarian cancer patients. The in-vitro and in-vivo data can be discussed in detail with the corresponding author.