Biological interactions in vitro of zinc oxide nanoparticles of different characteristics

Zinc oxide nanoparticles (ZnO NPs) have recently received growing attention for various biomedical applications, including use as therapeutic or carrier for drug delivery and/or imaging. For the above applications, the NPs necessitate administration into the body leading to their systemic exposure. To better anticipate the safety, make risk assessment, and be able to interpret the future preclinical and clinical safety data, it is important to systematically understand the biological interaction of the NPs, the consequences of such interaction, and the mechanisms associated with the toxicity induction, with the important components with which the NPs are expected to be in contact after systemic exposure. In this context, we report here a detailed study on the biological interactions in vitro of the ZnO NPs with healthy human primary lymphocytes as these are the important immune components and the first systemic immune contact, and with the whole human blood. Additionally, the influence, if any, of the NPs shape (spheres and rods) on the biological interaction has been evaluated. The ZnO NPs caused toxicity (30% at 12.5 μg ml−1 spheres and 10.5 μg ml−1 rods; 50% at 22 μg ml−1 spheres and 19.5 μg ml−1 rods) to the lymphocytes at molecular and genetic level in a dose-dependent and shape-dependent manner, while the interaction consequences with the blood and blood components such as RBC, platelets was only dose-dependent and not shape-dependent. This is evident from the decreased RBC count due to increased %Hemolysis (5.3% in both the spheres- and rods-treated blood) and decreased platelet count due to increased %platelet aggregation (28% in spheres-treated and 33% in rods-treated platelet-rich plasma). Such in-depth understanding of the biological interaction of the NPs, the consequences, and the associated mechanisms in vitro could be expected to allow anticipating the NP safety for risk assessment and for interpretation of the preclinical and clinical safety data when available.