Surface Control of Nanodiamond: From Homogeneous Termination to Complex Functional Architectures for Biomedical Applications.

Interest in nanodiamond (ND) has been spurred by its unique properties such as high biocompatibility, versatile surface chemistry, and the possibility to apply it as drug delivery agent, cross-linker, or coating and for sensing applications when luminescent lattice defects such as the NV centers are present in the crystal lattice. Currently, nanodiamond has been used for targeted drug delivery, phototherapeutic applications, and sensing and imaging in cellular environments and in vitro. Furthermore, suitably functionalized nanodiamond is a promising material for tissue engineering applications. However, the application of nanodiamond has long been hampered by a number of obstacles and challenges met with commercially available nanodiamonds of different origins. A major issue is related to the strong agglomeration of the individual particles resulting in covalently linked aggregates with larger sizes and a broad size distribution. Furthermore, the surface termination of typical nanodiamond particles tends to be rather inhomogeneous, containing a multitude of different functional groups. The retention of functionality of immobilized moieties for bioapplications is often not known. And finally, the surface of nanodiamond possesses a strong propensity for nonspecific interaction, especially proteins from serum, cell fluids, or the culture media used for the incubation of cells with nanodiamond. The resulting protein corona influences the possibility to access functional moieties on the diamond surface and leads to a reduced reproducibility of observations in physiological environments and a limited attribution of effects to the presence of the functional moieties on the diamond surface. In this Account, we describe our efforts to address these challenges using multiple strategies mainly for the example of detonation nanodiamond (DND). First, a homogeneous size distribution of the nanoparticles and an initial surface termination with a unique type of atoms or groups can be achieved using mechanochemical methods and treatments with different reagents in both solution and gas phases. Reactions in liquid media typically lead to more uniform results as the entire surface of the particles becomes equally accessible. We have then worked on the development of different covalent linker strategies to accommodate the grafting needs of different functional moieties and thus to enable the production of orthogonally functionalized ND particles, which can be modified with multiple moieties in a controlled fashion. The noncovalent immobilization of functional units is equally useful as it permits the conservation of functionality for sensitive proteins, which denature upon covalent immobilization. In summary, our work aims to gain full control over the surface properties of diamond nanoparticles and to develop a toolbox of chemical methods to provide functionalized and tailored nanodiamond for a plethora of biomedical applications. Further research in the field of diamond functionalization will cover also the transfer of already existing methods to other types of diamond surfaces, the production of stoichiometrically functionalized particles, the covalent and dynamic self-assembly of nanodiamond particles, and the continuing development of suitable characterization techniques.