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While the toxicity of metal-based nanoparticles (NP) has been investigated in an increasing number of studies, little is known about metal-based fibrous materials, so-called nanowires (NWs). Within the present study, the physico-chemical properties of particulate and fibrous nanomaterials based on Cu, CuO, Ni, and Ag as well as TiO2 and CeO2 NP were characterized and compared with respect to abiotic metal ion release in different physiologically relevant media as well as acellular reactivity. While none of the materials was soluble at neutral pH in artificial alveolar fluid (AAF), Cu, CuO, and Ni-based materials displayed distinct dissolution under the acidic conditions found in artificial lysosomal fluids (ALF and PSF). Subsequently, four different cell lines were applied to compare cytotoxicity as well as intracellular metal ion release in the cytoplasm and nucleus. Both cytotoxicity and bioavailability reflected the acellular dissolution rates in physiological lysosomal media (pH 4.5); only Ag-based materials showed no or very low acellular solubility, but pronounced intracellular bioavailability and cytotoxicity, leading to particularly high concentrations in the nucleus. In conclusion, in spite of some quantitative differences, the intracellular bioavailability as well as toxicity is mostly driven by the respective metal and is less modulated by the shape of the respective NP or NW.

Targeted tumor therapy can provide the basis for the inhibition of tumor growth. However, a number of toxin-based therapeutics lack efficacy because of insufficient endosomal escape after being internalized by endocytosis. To address this problem, the potential of glycosylated triterpenoids, such as SO1861, as endosomal escape enhancers (EEE) for superparamagnetic iron oxide nanoparticle (SPION)-based toxin therapy was investigated. Herein, two different SPION-based particle systems were synthesized, each selectively functionalized with either the targeted toxin, dianthin-epidermal growth factor (DiaEGF), or the EEE, SO1861. After applying both particle systems in vitro, an almost 2000-fold enhancement in tumor cell cytotoxicity compared to the monotherapy with SPION-DiaEGF and a 6.7-fold gain in specificity was observed. Thus, the required dose of the formulation was appreciably reduced, and the therapeutic window widened.