Aluminum enhances the oxidative damage of ZnO NMs in the human neuroblastoma SH-SY5Y cell line

Abstract

Bare and doped zinc oxide nanomaterials (ZnO NMs) are of great interest as multifunctional platforms for biomedical applications. In this study, we systematically investigate the physicochemical properties of Aluminum doped ZnO (AZO) and its bio-interactions with neuroblastoma (SH-SY5Y) and red blood (RBCs) cells. We provide a comprehensive chemical and structural characterization of the NMs. We also evaluated the biocompatibility of AZO NMs using traditional toxicity assays and advanced microscopy techniques. The toxicity of AZO NMs towards SH-SY5Y cells, decreases as a function of Al doping but is higher than the toxicity of ZnO NMs. Our results show that N-acetyl cysteine protects SH-SY5Y cells against reactive oxygen species toxicity induced by AZO NMs. ZnO and AZO NMs do not exert hemolysis in human RBCs at the doses that cause toxicity (IC50) in neuroblastoma cells. The Atomic force microscopy qualitative analysis of the interaction of SH-SY5Y cells with AZO NMs shows evidence that the affinity of the materials with the cells results in morphology changes and diminished interactions between neighboring cells. The holotomographic microscopy analysis demonstrates NMs' internalization in SH-SY5Y cells, changes in their chemical composition, and the role of lipid droplets in the clearance of toxicants. Graphical Abstract

Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research

“…HTM offers numerous advantages to advance live cell imaging: (a) high resolution (nanoscale), (b) label-free, (c) real-time, (d) quantitative phase imaging, (e) fluorescence. Figure 4 shows examples of HTM images of different kind of cells or organisms [ 4 , 5 ]. Figure 4 C1 shows a 3D representation of an A549 cell (control group).…”

“…White arrows indicate the presence of NMs in the bacterial cells. Figure 5 C and C1 show the effects of the interaction of ZnO-Al 3+ NMs and SHSY-5Y cells [ 4 ]. The control group (Fig.…”

“…The sequential use of these techniques results in a precise identification of different cellular organelles, super-resolution morphometric analysis, and study of the dynamics of biological processes. A late study shows a detailed investigation (that correlates traditional toxicity assays with AFM and HTM analysis) of the bioactivity of aluminum-doped zinc oxide using SH-SY5Y cells as biological model organisms [ 4 ].…”

“…Still, it only shows a low-resolution 2D perspective of cells and microorganisms. On the other hand, electron microscopies (i.e., scanning electron microscopy, SEM) render a more detailed view of the cell morphology [ 3 , 4 ]. However, this technique requires sample fixation and a conductive cover for imaging and is not suitable for analyzing living cells [ 3 ].…”

“…Combining data generated by HTM (3D and internal view of cells) and AFM (high-resolution surface analysis, mechanical properties) is essential for developing fields like cell pathology, cancer research, microbiology, nanotoxicology, and many others . We pursue to optimize the synthesis variables to render diverse nanomaterials (NMs) with tuned properties for biomedical or environmental remediation applications [ 4 – 6 ]. In addition, numerous research efforts aim to implement standard protocols to evaluate NMs´ bio-activity since these materials might enter living organisms accidentally or deliberately [ 7 ].…”