<strong>A New Active and Specific Diamond Nanoprobe Designed for Medical Imaging Applications</strong>

Abstract

The popularity of nanodiamonds has risen over the last few years because they have proved to be safe, biocompatible and significantly less toxic than other well-known carbon nanomaterials [1]. According to some studies, diamond nanoparticles seem to be a good candidate for biomedical purposes and more precisely as a tool for therapeutic and diagnosis applications in the medical imaging context [2, 3]. The main goal of this work is to validate an effective bimodal diamond-based nanoprobe for medical imaging techniques and specific of apoptosis. The functionalization of the platform involves the grafting of an optical agent (an amine-derivative of rhodamine), an apoptosis-specific vector (TLVSSL or E3 peptide), and a paramagnetic contrast agent (an amine-derivative of Gd-DOTA). The benefit of this multifunctional platform is the alliance of properties of magnetic resonance imaging (MRI) and optical imaging (OI) in terms of high spatial resolution and high sensitivity.                                                                                     In this work, an annealing process has been employed to saturate the surface in a uniform way with carboxylic acid groups. The carboxylated diamond platform (n-COOH) is the starting material which enables a high surface loading of specific molecules for biomedical applications. The atomic distribution of the n-COOH surface was analyzed by XPS to define the efficiency of the oxidation method. The quantitative determination of surface carboxyl groups added by the thermal treatment was performed by conductimetric titration measurements [4]. Parallel to the surface uniformity and the dispersion of nanoparticles in aqueous solution, a paramagnetic gadolinium complex (Gd-DOTA-NH2) has been synthesized in order to make the nanosystem active in MRI. The intermediate products of the synthesis have been characterized by mass spectrometry and NMR techniques. The relaxivity properties of the final complex were studied at 20 and 60 MHz and compared to the commercial complex, the Gd-DOTA. The successive couplings of the molecules of interest (fluorochrome, peptide, paramagnetic complex) with the carboxylated platform were performed in water via an EDC(/NHS)-coupling process. After intensive purification by dialysis, the efficiency of the new active and specific diamond nanoprobe as bimodal agent was assessed in terms of relaxometric properties and in vitro studies.   Zhang, X., et al., A comparative study of cellular uptake and cytotoxicity of multi-walled carbon nanotubes, graphene oxide, and nanodiamond. Toxicology Research, 2012. 1(1): p. 62-68. Manus, L.M., et al., Gd (III)-nanodiamond conjugates for MRI contrast enhancement. Nano letters, 2009. 10(2): p. 484-489. Chow, E.K., et al., Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Science translational medicine, 2011. 3(73): p. 73ra21-73ra21.       4. Schmidlin, L., et al., Identification, quantification and modification of detonation nanodiamond functional groups. Diamond and Related Materials, 2012. 22: p. 113-117.