Size, Surface Properties, and Ion Release of Zinc Oxide Nanoparticles: Effects on Cytotoxicity, Dopaminergic Gene Expression, and Acetylcholinesterase Inhibition in Neuronal PC-12 Cells.

The extensive applications of zinc oxide nanoparticles (ZnO NPs) have resulted in a substantial risk of human exposure. However, the knowledge of the toxicity of these NPs in the nervous system is still limited. A comparative analysis of ZnO NPs of various sizes and NPs of the same size, with and without surface coating, and the potential role of released zinc ions is yet to be thoroughly explored. As a result, we have studied the cellular toxicity of two different-sized ZnO NPs, ZnO-22 (22 nm) and ZnO-43 (43 nm), and NPs with similar size but with polyvinylpyrrolidone coating (ZnO-P, 45 nm). The findings from our study suggested a time-, size-, and surface coating-dependent cytotoxicity in PC-12 cells at a concentration ≥ 10 µg/ml. ZnO NP treatment significantly elevated reactive oxygen and reactive nitrogen species, thereby increasing oxidative stress. The exposure of ZnO-22 and ZnO-43 significantly upregulated the expression of monoamine oxidase-A and downregulated the α-synuclein gene expression associated with the dopaminergic system. The interaction of NPs enzymes in the nervous system is also hazardous. Therefore, the inhibition activity of acetylcholinesterase enzyme was also studied for its interaction with these NPs, and the results indicated a dose-dependent inhibition of enzyme activity. Particle size, coating, and cellular interactions modulate ZnO NP's cytotoxicity; smaller sizes enhance cellular uptake and reactivity, while coating reduces cytotoxicity by limiting direct cell contact and potentially mitigating oxidative stress. Furthermore, the study of released zinc ions from the NPs suggested no significant contribution to the observed cytotoxicity compared to the NPs.

Comprehensive Analysis of Titanium Oxide Nanoparticle Size and Surface Properties on Neuronal PC-12 Cells: Unraveling Cytotoxicity, Dopaminergic Gene Expression, and Acetylcholinesterase Inhibition.

Titanium oxide nanoparticles can penetrate the blood-brain barrier, infiltrate the central nervous system, and induce neurotoxicity. One of the most often utilized nanoparticles has been investigated for their neurotoxicity in many studies. Nonetheless, there remains an unexplored aspect regarding the comparative analysis of particles varying in size and nanoparticles of identical dimensions, both with and devoid of surface coating. In the current study, we synthesized two differently sized nanoparticles, TiO2-10 (10 nm) and TiO2-22 (22 nm), and nanoparticles of the same size but with a polyvinylpyrrolidone surface coating (TiO2-PVP, 22 nm) and studied their toxic effects on neural PC-12 cells. The results highlighted significant dose- and time-dependent cytotoxicity at concentrations ≥10 µg/mL. The exposure of TiO2 nanoparticles significantly elevated reactive oxygen and nitrogen species levels, IL-6 and TNF-α levels, altered the mitochondrial membrane potential, and enhanced apoptosis-related caspase-3 activity, irrespective of size and surface coating. The interaction of the nanoparticles with acetylcholinesterase enzyme activity was also investigated, and the results revealed a dose-dependent suppression of enzymatic activity. However, the gene expression studies indicated no effect on the expression of all six genes associated with the dopaminergic system upon exposure to 10 µg/mL for any nanoparticle. The results demonstrated no significant difference between the outcomes of TiO2-10 and TiO2-22 NPs. However, the polyvinylpyrrolidone surface coating was able to attenuate the neurotoxic effects. These findings suggest that as the TiO2 nanoparticles get smaller (towards 0 nm), they might promote apoptosis and inflammatory reactions in neural cells via oxidative stress, irrespective of their size.

Toxic implications of silver nanoparticles on the central nervous system: A systematic literature review.

Silver nanoparticles have many medical and commercial applications, but their effects on human health are poorly understood. They are used extensively in products of daily use, but little is known about their potential neurotoxic effects. A xenobiotic metal, silver, has no known physiological significance in the human body as a trace metal. Biokinetics of silver nanoparticles indicates its elimination from the body via urine and feces route. However, a substantial amount of evidence from both in vitro and in vivo experimental research unequivocally establish the fact of easier penetration of smaller nanoparticles across the blood-brain barrier to enter in brain and thereby interaction with cellular components to induce neurotoxic effects. Toxicological effects of silver nanoparticles rely on the degree of exposure, particle size, surface coating, and agglomeration state as well as the type of cell or organism used to evaluate its toxicity. This review covers pertinent facts and the present state of knowledge about the neurotoxicity of silver nanoparticles reviewing the impacts on oxidative stress, neuroinflammation, mitochondrial function, neurodegeneration, apoptosis, and necrosis. The effect of silver nanoparticles on the central nervous system is a topic of growing interest and concern that requires immediate consideration.

Pharmacokinetics, Metabolism, Distribution and Permeability of Nanomedicine.

BACKGROUND: Medical application of nanotechnology is termed as Nanomedicine and is widely used in healthcare industries. Nanotechnology has helped Physicians, Scientists and Technologists to understand the changes in cellular levels to develop nanomedicines and address the challenges faced by the healthcare sectors. Nanoparticles with less than 1nm in size have been used as drug delivery and gene delivery systems to accelerate the drug action in humans. Size of nanomaterials is akin to that of biomolecules and expected to have better interactions. Hence, its utility for various biomedical applications is explored. OBJECTIVE: Pharmacokinetics, metabolism, permeability, distribution and elimination studies of nanoparticles are essential to understand its potency, toxicity threshold and confirm its safe use in humans. Reports were available for toxicity studies on nanoparticles, but work on metabolism, pharmacokinetics, distribution and permeability of nanomedicine is limited. Hence, the main focus of this review article is about metabolism, pharmacokinetics, permeability and biodistribution of nanomaterials used in nanomedicine. CONCLUSION: Nanomedicine is increasingly becoming important in the treatment of diseases and diagnosis. Size of the particle plays an important role. As the particle size decreases its effect to cure the disease increases. Pharmacokinetics, bioavailability, half-life, metabolism, biodistribution and permeability of nanomedicine were found to be better than that of microsized drugs. In vitro and In vivo ADME (Absorption, Distribution, Metabolism and Excretion) studies are mandatory for pharmaceutical organic drugs. Similarly, nanomaterials should be subjected to both in vitro and in vivo ADME studies. Thus, nanomedicine can assist in the development of safe personalized medicine in humans.