Nanodiamond (ND) is a versatile and promising material for bioapplications. Despite many efforts, agglomeration of nanodiamond and the nonspecific adsorption of proteins on the ND surface when exposed to biofluids remains a major obstacle for biomedical applications. Here, the functionalization of detonation nanodiamond with zwitterionic moieties in combination with tetraethylene glycol (TEG) moieties immobilized by click chemistry to improve the colloidal dispersion in physiological media with strong ion background and for the simultaneous prevention of nonspecific interactions with proteins is reported. Based on five building blocks, a series of ND conjugates is synthesized and their performance is compared in biofluids, such as fetal bovine serum (FBS) and Dulbecco's modified Eagle medium (DMEM). The adsorption of proteins is investigated via dynamic light scattering (DLS) and thermogravimetric analysis. The colloidal stability is tested with DLS monitoring over prolonged periods of time in various ratios of water/FBS/DMEM and at different pH values. The results show that zwitterions efficiently promote the anti-fouling properties, whereas the TEG linker is essential for the enhanced colloidal stability of the particles.
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