Interactions of Zinc Oxide Nanostructures with Mammalian Cells: Cytotoxicity and Photocatalytic Toxicity

Abstract

This article presents a state-of-the-art review and analysis of literature studies on the morphological structure, fabrication, cytotoxicity, and photocatalytic toxicity of zinc oxide nanostructures (nZnO) of mammalian cells. nZnO with different morphologies, e.g., quantum dots, nanoparticles, nanorods, and nanotetrapods are toxic to a wide variety of mammalian cell lines due to in vitro cell–material interactions. Several mechanisms responsible for in vitro cytotoxicity have been proposed. These include the penetration of nZnO into the cytoplasm, generating reactive oxygen species (ROS) that degrade mitochondrial function, induce endoplasmic reticulum stress, and damage deoxyribonucleic acid (DNA), lipid, and protein molecules. Otherwise, nZnO dissolve extracellularly into zinc ions and the subsequent diffusion of ions into the cytoplasm can create ROS. Furthermore, internalization of nZnO and localization in acidic lysosomes result in their dissolution into zinc ions, producing ROS too in cytoplasm. These ROS-mediated responses induce caspase-dependent apoptosis via the activation of B-cell lymphoma 2 (Bcl2), Bcl2-associated X protein (Bax), CCAAT/enhancer-binding protein homologous protein (chop), and phosphoprotein p53 gene expressions. In vivo studies on a mouse model reveal the adverse impacts of nZnO on internal organs through different administration routes. The administration of ZnO nanoparticles into mice via intraperitoneal instillation and intravenous injection facilitates their accumulation in target organs, such as the liver, spleen, and lung. ZnO is a semiconductor with a large bandgap showing photocatalytic behavior under ultraviolet (UV) light irradiation. As such, photogenerated electron–hole pairs react with adsorbed oxygen and water molecules to produce ROS. So, the ROS-mediated selective killing for human tumor cells is beneficial for cancer treatment in photodynamic therapy. The photoinduced effects of noble metal doped nZnO for creating ROS under UV and visible light for killing cancer cells are also addressed.

CdSe/ZnS Core-Shell-Type Quantum Dot Nanoparticles Disrupt the Cellular Homeostasis in Cellular Blood–Brain Barrier Models

“…Our main object of the studies was core-shell (cadmium selenide and zinc sulfide, respectively) quantum dot nanoparticles, synthesized and exploited industrially mainly due to their quantum state-related optical and electronic properties. Their physico-chemical characteristics which were most relevant to our study are their relatively small size (average diameter 6.2 nm), allowing for their potentially efficient cellular uptake both by triggered endocytosis and more passively by macropinocytosis [ 22 , 23 ]; poly-anionic carboxyl group surface modification, providing potential mechanisms of escape to cytoplasm [ 24 ]; and adsorptive interactions with important cellular components, including proteins [ 25 ] and mitochondrial lipids [ 26 ]; and the inclusion of two heavy metal elements in their structure, cadmium (in the core) and zinc (in the shell), which both have a plethora of known toxicological effects when in the form of free ions [ 27 ]. These QDs have a broad technological and biotechnological application range, extensively reviewed in [ 28 ], encompassing transistor and semiconductor nanoelectronics fabrication, production of lasers, solar cells and light-emitting diodes, medical imaging, and drug delivery.…”

Comparison of cytotoxicity of Ag/ZnO and Ag@ZnO nanocomplexes to human umbilical vein endothelial cells in vitro

“…ZnO NPs are partially soluble to release Zn ions (J. Liu et al, 2016). Indeed, extensive studies suggested that ZnO‐based NPs induced cytotoxicity by inducing excessive intracellular Zn ions due to the dissolution of ZnO (Gong, Ji, Liu, Li, & Cao, 2017; Liao, Jin, Li, & Tjong, 2020; Yan et al, 2019). Consistently, here, we found that Ag/ZnO, Ag@ZnO, and ZnO NPs only significantly promoted intracellular Zn ions at cytotoxic concentrations (Figure S3), which indicated a role of excessive Zn ions in cytotoxicity of NPs.…”

Fabrication of reusable polymer nanocomposite films made of thermoplastic polyurethane and modified BiVO4 for photodegradation of Malachite Green

“…They further react as explained in the following reactions to generate the reactive species. These active species further interact with the dye molecules and degradation of malachite green is carried out [47][48][49].…”