Routes to Control the Chemical Potential and to Modulate the Reactivity of Nanodiamond Surfaces

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Routes to Control the Chemical Potential and to Modulate the Reactivity of Nanodiamond Surfaces Giacomo Reina1, Silvia Orlanducci1, Stefano Gay1, Angelo Gismondi2, Teresa Lavecchia1, Maria Letizia Terranova1, Emanuela Tamburri1 1 Dept. Science and Chemical Technology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, Rome 00133, Italy 2 Dept. of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, Rome 00133, Italy ABSTRACT The use of detonation nanodiamond (DND) for drug delivery and cell-imaging is grounded on its chemical functionalization, and the key task to be addressed is the capability to simplify the process steps, to reduce the process times and to maximize the drug/ligand uptake. The idea underlying the present research is to modulate the loading capability of DND by controlled modification of the surface organic groups. To this aim the DND samples are treated either by wet chemistry, using medium-strong reducing agents, or by tunable H-plasmas produced in a custom-designed MW-RF reactor. The affinity of the treated DND surfaces for drugs has been probed by conjugating the ciproten (5,7- dimethoxycoumarin), a natural antioxidant molecule, and by testing in vitro the feasibility to use coumarin vehicled by nanodiamond (C@DND) as chemioterapeutic drug. The methodologies developed to modify the DND surfaces are offering practical solutions to the still open problems related to DND-based systems for drug delivery applications. INTRODUCTION Over the last years, the scientific community is increasingly turning its attention towards detonation nanodiamond (DND). [1-6] DND are produced from the detonation of TNT and RDX under strict conditions [7]. This material bares the well-known bulk diamond properties, like hardness, mechanical resistance and stiffness, and several other features due to its nanosized dimensions. DND consists of: a core made of sp3 carbon with a typical size from 2 to 8 nm a first shell mainly composed by sp2 carbon and an other shell rich in organic groups [8-9]. Several studies have been reported on the covalent functionalization of nanodiamonds [10-13]. The developing of various classes of reaction on DND surface has allowed nanodiamonds to be easily incorporated in many polymeric matrices and therefore to be used in various applications: from organic electronics to thermal management [14-17]. More recently different studies successfully demonstrated the use of detonation nanodiamonds in biological fields [18-22]. Indeed DND bares the lowest cytotoxicity among all the carbon nanostructures, moreover the diamond nanograins are able to easily enter in the cells. Those facts make DND an ideal material for drug delivery application. Recently we demonstrated how DND can be used for the delivery of natural molecules (ciproten and quercetin) for cancer treatments [24]. In particular we made clear how chemical modifications of nanodiamond surfaces play a fundamental role in modulating the biological effects of the transported molecules. In this paper we repo