Unveiling the nanotoxicological aspects of Se nanomaterials differing in size and morphology

Although the general concept of nanotechnology relies on exploitation of size-dependent properties of nanoscaled materials, the relation between the size/morphology of nanoparticles with their biological activity remains not well understood. Therefore, we aimed at investigating the biological activity of Se nanoparticles, one of the most promising candidates of nanomaterials for biomedicine, possessing the same crystal structure, but differing in morphology (nanorods vs. spherical particles) and aspect ratios (AR, 11.5 vs. 22.3 vs. 1.0) in human cells and BALB/c mice. Herein, we report that in case of nanorod-shaped Se nanomaterials, AR is a critical factor describing their cytotoxicity and biocompatibility. However, spherical nanoparticles (AR 1.0) do not fit this statement and exhibit markedly higher cytotoxicity than lower-AR Se nanorods. Beside of cytotoxicity, we also show that morphology and size substantially affect the uptake and intracellular fate of Se nanomaterials. In line with in vitro data, in vivo i.v. administration of Se nanomaterials revealed the highest toxicity for higher-AR nanorods followed by spherical nanoparticles and lower-AR nanorods. Moreover, we revealed that Se nanomaterials are able to alter intracellular redox homeostasis, and affect the acidic intracellular vesicles and cytoskeletal architecture in a size- and morphology-dependent manner. Although the tested nanoparticles were produced from the similar sources, their behavior differs markedly, since each type is promising for several various application scenarios, and the presented testing protocol could serve as a concept standardizing the biological relevance of the size and morphology of the various types of nanomaterials and nanoparticles.