Final Report Summary - UHMSNMRI (Design and testing of Gd3+-Loaded Ultrasmall Hollow Mesoporous Silica Nanosphere Platform as High Sensitivity Probes for Targeted Magnetic Resonance Imaging of Tumor In Vivo) Magnetic resonance imaging (MRI) has become a powerful technique in diagnostic clinical medicine and biomedical research by providing long-term, high spatial resolution images of soft tissue without exposing to ionizing radiation. However, MRI still suffers from a relatively low sensitivity and in one third of all MRI clinic scans contrast agents (CAs) are needed. Therefore, the development of highly efficient CAs has been an object of great interest to improve the MR sensitivity. Herein, we developed a targeting, high relaxivity, fluorimagnetic nanoprobe based on fluorescein-doped and amino-functionalized small size mesoporous silica nanoparticles (MSNs) (~ 30 nm). The fluorescein dye (FITC) was embedded in the framework of the silica by co-condensation with a modified silicate source, endowing the MSNs with fluorescent properties in order to visualize the interaction of the MSNs with cells. The MSNs surface was further functionalized with macrocyclic Gd-complexes: Gd-DOTAGA and the αvβ3 integrin targeting ligand RGD peptide. The final nanoprobe (Gd-MSNs-RGD) showed good physiological stability and high relaxivity (37.6 mM-1s-1 at 21.5 MHz). The cytotoxicity and targeting capability of the Gd-MSNs-RGD nanoprobes were first evaluated in human malignant gliomas U87MG cells (which overexpress integrin αvβ3 receptors) by fluorescence and MR imaging. The Gd-MSNs-RGD showed very low cytotoxicity and highly specificity binding affinity to integrin-positive U87MG cells in vitro. Then, the Gd-MSNs-RGD nanoprobes were tested fro the visualization of xenografts tumor models. The in vivo MR images clearly highlighted the tumor from 1 to 6 hours after intravenous administration. These results were further confirmed by the ex vivo fluorescence imaging of major organs. In conclusion, our results have successfully demonstrated the application of integrin αvβ3 targeting Gd-MSNs-RGD for high sensitive multifunctional imaging studies, from the cellular scale to small-animal whole-body evaluation. Related documents final1-attachment.pdf
