Nanoparticles (NP) are currently the subject of active researches in the context of medical imaging. The possibilities of applications are numerous and the versatility of these nanoparticles allows their modulations to serve as imaging probes (diagnostic), drug-delivery vectors (therapeutic) or both (theranostic). The main objective of this work is to develop and characterize an effective multimodal nanodiamond-based probe for medical imaging and specific of apoptosis. The functionalization of the platform involves the grafting of an apoptosis-specific vector, an optical agent and a paramagnetic complex.The first part of this work consisted in the characterization of the platform based on nanodiamond powder with size (DLS, TEM and XRD), morphology (SEM), stability and physicochemical analysis methods (turbidimetry and FTIR). Then, an oxidation step was performed in order to increase the number of carboxylic groups on the NP surface. The analysis of the TEM pictures confirmed that the oxidative treatment induced a size-reduction of nanodiamonds in solution.The second part concerned the preparations of the specific peptide andthe paramagnetic complex. The synthesis of the peptide was carried out using an automated synthesizer and its structure was confirmed by mass spectrometry and NMR. The ligand derived from DOTA was synthesized starting from N6-carbobenzyloxy-L-Lysine and cyclen and then complexed with gadolinium chloride to provide the paramagnetic complex. The characterization by relaxometry and NMRD profiles has proved the efficiency of this new complex as T1agent.The last step of the work has been dedicated to the development and characterization of the new multimodal probes. Two samples of diamond NP have been reserved for the grafting of the apoptosis-specific vector and one of the optical agents (fluorescein trifluoroacetate or methyl violet). A third sample of NP was grafted with the MRI contrast agent.In conclusion, the coupling of the platform with fluorescein has been demonstrated by fluorescence spectroscopy. In addition, optical microscopy study conducted on cell cultures gave evidence of the efficiency of graftings. Indeed, the experiments demonstrated the affinity of NP with Jurkat cells stimulated by anti-Fas. Results demonstrated clearly the effectiveness of the MRI nanodiamond-based probe for medical imaging.

New multimodal platforms of nanodiamond for molecular imaging

247th National Meeting (2014)

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