Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications.

The advance of reliable and eco-friendly strategies for the development of nanoparticles is a fundamental key to the discipline of nanotechnology. Nanoparticles have been continuously evaluated and have been used in many industrial applications for a decade. In particular, the role of zinc oxide nanoparticles (ZnO NPs) has received a great interest because of various properties such as UV filter properties and photochemical, antifungal, high catalyst, and antimicrobial activities. Because of the high rate of poisonous chemicals and the extreme surroundings used within the chemical and physical methods, the green techniques have been adopted using plants, fungi, bacteria, and algae for the synthesis of nanoparticles. Therefore, this paper considers various green synthesis methods to provide the evidence of ZnO NP role to several applications, and in addition, biomedical applications and toxic effect were reviewed. Therefore, the paper used various secondary sources to collect the relevant review articles. From the findings, the green route of synthesis is rather safe and eco-friendly when compared to physical and chemical means of synthesis. On the other hand, its biomedical applications in this sector are increased day by day in various processes including bioimaging, drug delivery, biosensors, and gene delivery. With respect to its toxicity properties, ZnO NPs can act as smart weapons against multiple drug-resistant microorganisms and as a talented substitute for antibiotics.

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A Review on Green Synthesis, Biomedical Applications, and Toxicity Studies of ZnO NPs

Nanoparticles (NPs) are currently used in diagnosis and treatment of many human diseases, including autoimmune diseases and cancer. However, cytotoxic effects of NPs on normal cells and living organs is a severe limiting factor that hinders their use in clinic. In addition, diversity of NPs and their physico-chemical properties, including particle size, shape, surface area, dispersity and protein corona effects are considered as key factors that have a crucial impact on their safe or toxicological behaviors. Current studies on toxic effects of NPs are aimed to identify the targets and mechanisms of their side effects, with a focus on elucidating the patterns of NP transport, accumulation, degradation, and elimination, in both in vitro and in vitro models. NPs can enter the body through inhalation, skin and digestive routes. Consequently, there is a need for reliable information about effects of NPs on various organs in order to reveal their efficacy and impact on health. This review covers the existing knowledge base on the subject that hopefully prepares us better to address these challenges.

Health Concerns of Various Nanoparticles: A Review of Their in Vitro and in Vivo Toxicity.

Background Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient. Methods In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster. A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs. Results For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript (DDIT3) and endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production. Conclusion The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in vivo. More extensive studies would be needed to verify the safety issues related to increased usage of ZnO NPs by consumers.

Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster.

Nanotechnology had matured significantly during the last two decades as it has transitioned from bench top science to applied technology. Even though the issue of safety of nanotechnology has been raised nearly one decade ago, the rapid progress in development and use of nanomaterials has not yet been matched by toxicological investigations. Many recent studies have simply outlined the toxic effects of nanoparticles (NPs), but few have systematically addressed their potentially adverse biological effects on target organs. Some animal models have shown that NPs could be accumulated in various organs. These accumulations can access the vasculature and target other organs, resulting in a potential health risks. After the brief description of current knowledge on the wide applications of several common NPs, their applications and the toxicokinetics, this review focused on effects of NPs on organ functions and mammal health after acute or chronic exposure, and potential mechanisms of action. Due to their physical properties, the liver, kidneys and lung are the main target organs of NPs. Most of NPs show slight toxicity when exposed to animals, while certain toxic effects like oxidative stress generation, inflammation and DNA damage are commonly observed. The severity of NPs toxicity is dependent upon several factors, including exposure dose and administration, NPs chemistry, size, shape, agglomeration state, and electromagnetic properties, which could provide useful information necessary to control the toxicity of NPs. Finally, the safety evaluation of nanotoxicity was addressed.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jat.3499

Review of the effects of manufactured nanoparticles on mammalian target organs

Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[−]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(−) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg.

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Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

Purpose
The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM20(+)) nanoparticles in Sprague Dawley rats for 90 days.

https://www.dovepress.com/getfile.php?fileID=22871

Geon Yong Kim

Papers

Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats.