Aqueous dispersions of functionalized carbon nanotubes (CNTs) are now widely used for biomedical applications. Their stability in different in vitro or in vivo environments, however, depends on a wide range of parameters, such as pH and salt concentrations of the surrounding medium, and length, aspect ratio, surface charge, and functionalization of the applied CNTs. Although many of these aspects have been investigated separately, no study is available in the literature to date, which examines these parameters simultaneously. Therefore, we have chosen five types of carbon nanotubes, varying in their dimensions and surface properties, for a multidimensional analysis of dispersion stability in salt solutions of differing pH and concentrations. Furthermore, we examine the dispersion stability of oxidized CNTs in biological fluids, such as cellular growth media and human plasma, and their toxicity toward cancer cells. To enhance dispersibility and biocompatibility, the influence of different functionalization schemes is studied. The results of our investigations indicate that both CNT dimensions and surface functionalization have a significant influence on their dispersion and in vitro behavior. In particular, factors such as a short aspect ratio, presence of oxidation debris and serum proteins, low salt concentration, and an appropriate pH are shown to improve the dispersion stability. Furthermore, covalent surface functionalization with amine-terminated polyethylene glycol (PEG) is demonstrated to stabilize CNT dispersions in various media and to reduce deleterious effects on cultured cells. These findings provide crucial data for the development of biofunctionalization protocols, for example, for future cancer theranostics, and optimizing the stability of functionalized CNTs in varied biological environments.
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