Toxicity Of Metal Nanoparticles Research Articles

Challenges and Opportunities Associated With Drug Delivery for the Treatment of Solid Tumors.

In this review, we discuss the effectiveness of drug delivery system based on metal nanoparticles, and also, describe the problems associated with their delivery to tumor cells. Throughout recent years, more reports have appeared in the literature that demonstrate promising results for the treatment of various types of cancer using metal-based nanoparticles. Due to their unique physical and chemical properties, metal nanoparticles are effectively being used for the delivery of drug to the tumor cells, for cancer diagnosis and treatment. They can also be synthesized allowing the control of size and shape. However, the effectiveness of the metal nanoparticles for cancer treatment largely depends on their stability, biocompatibility, and ability to selectively affect tumor cells after their systemic or local administration. Another major problem associated with metal nanoparticles is their ability to overcome tumor tissue barriers such as atypical blood vessel structure, dense and rigid extracellular matrix, and high pressure of tumor interstitial fluid. The review also describes the design of tumor drug delivery systems that are based on metal nanoparticles. The mechanism of action of metal nanoparticles on cancer cells is also discussed. Considering the therapeutic safety and toxicity of metal nanoparticles, the prospects for their use for future clinical applications are being currently reviewed.

The Exposure and Hazards of Zinc Oxide Nanoparticles: In Vitro and In Vivo Studies

Background: Extensive application of zinc oxide nanoparticles has increased the likelihood of its release into the environment and subsequent human exposure and toxicity. The toxicity is thought to be a combined effect of intracellular particles and the release of dissolved zinc ions. Objectives: This review outlines the possible mechanisms of zinc oxide toxicity in biological organs through in vitro and in vivo experiments. Methods: We reviewed articles published between 2001 and 2021. In this way, we did a manual search of Google Scholar and scientific databases, including PubMed, Web of Science, Scopus, and Embase, with keywords such as “zinc oxide nanoparticles”, “toxicity mechanism”, and “in vivo and in vitro studies”. The other qualified papers contained the history of identifying zinc oxide nanoparticles, the toxicity of metallic nanoparticles, and physical, chemical, and biological side effects with topical and systematic approaches. Results: The main mechanism suggested for zinc-based nanoparticles-induced cell damage is via the induction of increased levels of reactive oxygen species, which are oxidative stress markers. This mechanism has also been found to be a key mechanism for the cytotoxicity of other metal nanomaterials. Zinc-based nanoparticles were found to induce oxidative DNA damage, inflammation, progressive degenerative cell changes, cell cycle arrest, cytogenetic alterations, and ROS-triggered mitochondria-mediated apoptosis in human organs. Conclusion: This review sheds light on the full understanding of in vitro and in vivo toxicity assessment of zinc oxide nanoparticles, highlighting the health concerns from the perspective of ZnO nanoparticles release to the ecosystem after their increasing application.

A Perspective on Therapeutic Applications and Strategies to Mitigate Toxicity of Metallic Nanoparticles.

Metallic nanoparticles (MNPs) have been widely used for diagnostic and therapeutic purposes in clinical practice. A number of MNP formulations are being investigated in clinical trials for various applications. This increase in the use of NPs results in higher exposure to humans, leading to toxicity issues. Hence, it is necessary to determine the possible undesirable effects of the MNPs after in-vivo application and exposure. One of the main reasons for the toxicity of MNPs is the release of their respective metallic ions throughout the body. Many research studies are in progress investigating the various strategies to reduce the toxicity of MNPs. These research studies aim to change the size, dose, agglomeration, release, and excretion rates of MNPs. In this perspective review, we discussed the possible strategies to improve the therapeutic effects of MNPs through various processes, with lessons learned from the studies involving silver nanoparticles (AgNPs). We also discussed the ways to manage the toxicity of MNPs by purification, surface functionalization, synergistic effect, and targeted therapy approach. All these strategies could reduce the dose of the MNPs without compromising their therapeutic benefits, which could decrease the toxicity of MNPs. Additionally, we briefly discussed the market and toxicology testing for FDA-regulated MNPs.

Undesirable consequences of the metallic nanoparticles action on the properties and functioning of Escherichia coli, Bacillus cereus and Staphylococcus epidermidis membranes

Controversial and inconsistent findings on the toxicity of metallic nanoparticles (NPs) against many bacteria are common in recorded studies; therefore, further advanced experimental work is needed to elucidate the mechanisms underlying nanotoxicity. This study deciphered the direct effects of Ag-NPs, Cu-NPs, ZnO-NPs and TiO2-NPs on membrane permeability, cytoplasmic leakage, ATP level, ATPase activity and fatty acid profiling of Escherichia coli, Bacillus cereus and Staphylococcus epidermidis as model microorganisms. A multifaceted analysis of all collected results indicated the different influences of individual NPs on the measured parameters depending on their type and concentration. Predominantly, membrane permeability was correlated with increased cytoplasmic leakage, reduced total ATP levels and ATPase activity. The established fatty acid profiles were unique and concerned various changes in the percentages of hydroxyl, cyclopropane, branched and unsaturated fatty acids. Decisively, E. coli was more susceptible to changes in measured parameters than B. cereus and S. epidermidis. Also, it was established that ZnO-NPs and Cu-NPs had a major differentiating impact on studied parameters. Additionally, bacterial cell imaging using scanning electron microscopy elucidated different NPs distributions on the cell surface. The presented results are believed to provide novel, valuable and accumulated knowledge in the understanding of NPs action on bacterial membranes.

New aspects of lipopeptide-incorporated nanoparticle synthesis and recent advancements in biomedical and environmental sciences: a review.

The toxicity of metal nanoparticles has introduced promising research in the current scenario since an enormous number of people have been potentially facing this problem in the world. The extensive attention on green nanoparticle synthesis has been focussed on as a vital step in bio-nanotechnology to improve biocompatibility, biodegradability, eco-friendliness, and huge potential utilization in various environmental and clinical assessments. Inherent influence on the study of green nanoparticles plays a key role to synthesize the controlled and surface-influenced molecule by altering the physical, chemical, and biological assets with the provision of various precursors, templating/co-templating agents, and supporting solvents. However, in this article, the dominant characteristics of several kinds of lipopeptide biosurfactants are discussed to execute a critical study of factors affecting synthesis procedure and applications. The recent approaches of metal, metal oxide, and composite nanomaterial synthesis have been deliberated as well as the elucidation of the reaction mechanism. Furthermore, this approach shows remarkable boosts in the production of nanoparticles with the very less employed harsh and hazardous processes as compared to chemical or physical method-based nanoparticle synthesis. This study also shows that the advances in strain selection for green nanoparticle production could be a worthwhile and strong economical approach in futuristic medical science research.

Effect of Titanium, Silver and Zinc Nanoparticles on Microalgae in the Aquatic Environment

Metallic nanoparticles (MNPs) are commonly incorporated in products found in households, industries, and agriculture. The presence of MNPs in the aquatic environment causes damage to living organisms and pollutes the water body rendering it harmful for human consumption. Several studies have been made on the toxicity of MNPs toward microalgae. Most of these studies reported changes in the cellular structure, growth rate, pigments, proteins, and enzymatic activity of microalgae. This review paper focuses on the toxic effects of titanium, zinc, and silver nanoparticles on microalgae in the aquatic environment. A better understanding of the behavior of MNPs in the ecosystem will allow scientists to produce environmentally safe MNPs.

A Critical Review on The Integration of Metal Nanoparticles in Biopolymers: An Alternative for Active and Sustainable Food Packaging

The use of plastic polymers in food packaging causes serious environmental and health problems and as a result, natural biopolymers are being developed (NBPs). Although NBPs have several shortcomings as a packaging material, these can be overcome with the help of nanotechnology. In this context, this review will report on the main findings about the effect of the integration of metal nanoparticles (MNPs) on the characteristics of NBPs. A systematic review was carried out using PRISMA methodology to select relevant studies from the last 5 years. According to the analysis performed, MNPs provide NBPs with a broad spectrum against bacteria, fungi and even viruses of interest. MNPs have also been shown to improve the physical, mechanical, optical, antioxidant and barrier characteristics of NBPs. MNPs are used at low concentrations (generally 0.5 to 5%) and this avoids their potential toxicity. MNPs are shown to be efficient materials to obtain bionanocomposites suitable for active food packaging. Studies focusing on the control of the antimicrobial effect of MNPs on desirable microorganisms are suggested. In addition, further studies on the evaluation of the potential toxicity of MNPs are needed to ensure food quality and safety.

Effect of Chlamydomonas reinhardtii on the fate of CuO nanoparticles in aquatic environment

In this study, the effect of Chlamydomonas reinhardtii on the fate of CuO nanoparticles (CuO-NPs) in aquatic environment were investigated in terms of the colloidal stability, the free Cu2+ releasing, extracellular adsorption Cu (Cuex) and intracellular assimilation Cu (Cuin). The results showed that, with the increasing microalgal density, the absolute value of zeta potential of CuO-NPs decreased and the mean hydrodynamic diameter (MHD) became larger, leading to a better aggregation and settling behavior of CuO-NPs. The microalgae also promoted the free Cu2+ releasing, however, inhibited adsorption and assimilation of metal nanoparticles (MNPs) into microalgal cells, resulting in the reduction of the Cuex and Cuin per microalgal cell. The phenomenon was probably due to the reduced chance of contact between microalgae and MNPs. The internalization of CuO-NPs was also observed in microalgal cells by high resolution transmission electron microscope (HRTEM). Furthermore, the results of fast fourier transform (FFT)/inversed FFT (IFFT) analysis indicated that the CuO-NPs was reduced to Cu2O-NPs in the microalgae cells. The above results suggested that the microalgae can significantly affect the fate of MNPs, and subsequently, influencing the bioavailability and toxicity of MNPs in the aquatic environment.

Toxicity of metallic nanoparticles in the central nervous system

Abstract Metallic nanoparticles due to their small size and unique physico-chemical characteristics have found excellent applications in various branches of industry and medicine. Therefore, for many years a growing interest has been observed among the scientific community in the improvement of our understanding of the impact of nanoparticles on the living organisms, especially on humans. Considering the delicate structure of the central nervous systemit is one of the organs most vulnerable to the adverse effects of metallic nanoparticles. For that reason, it is important to identify the modes of exposure and understand the mechanisms of the effect of nanoparticles on neuronal tissue. In this review, an attempt is undertaken to present current knowledge about metallic nanoparticles neurotoxicity based on the selected scientific publications. The route of entry of nanoparticles is described, as well as their distribution, penetration through the cell membrane and the blood-brain barrier. In addition, a study on the neurotoxicity in vitro and in vivo is presented, as well as some of the mechanisms that may be responsible for the negative effects of metallic nanoparticles on the central nervous system. Graphical abstract: This review summarizes the current knowledge on the toxicity of metallic NPs in the brain and central nervous system of the higher vertebrates.

The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes.

Metallic nanoparticles (MNPs) are new engineering materials with broad prospects for biomedical applications; thus, their biosafety has drawn great concern. The liver is the main detoxification organ of vertebrates. However, many issues concerning the interactions between MNPs and biological systems (cells and tissues) are unclear, particularly the toxic effects of MNPs on hepatocytes and other liver cells. Numerous researchers have shown that some MNPs can induce decreased cell survival rate, production of reactive oxygen species (ROS), mitochondrial damage, DNA strand breaks, and even autophagy, pyroptosis, apoptosis, or other forms of cell death. Our review focuses on the recent researches on the liver toxicity of MNPs and its mechanisms at cellular and subcellular levels to provide a scientific basis for the subsequent hepatotoxicity studies of MNPs.

Combined Effects of Test Media and Dietary Algae on the Toxicity of CuO and ZnO Nanoparticles to Freshwater Microcrustaceans Daphnia magna and Heterocypris incongruens: Food for Thought.

The chemical composition of the test medium as well as the presence of algae (microcrustaceans’ food) affects the bioavailability and thus the toxicity of metal nanoparticles (NP) to freshwater microcrustaceans. This study evaluated the effect of the addition of algae (Rapidocelis subcapitata at 7.5 × 106 cells/mL) on the toxicity of CuO (primary size 22–25 nm) and ZnO NP (10–15 nm) to planktic Daphnia magna and benthic Heterocypris incongruens in artificial (mineral) and natural freshwater (lake water). The toxicity of ionic controls, CuSO4 and ZnSO4, was evaluated in parallel. When algae were added and the toxicity was tested in mineral medium, 48 h EC50 of CuO and ZnO NP to D. magna was ~2 mg metal/L and 6-day LC50 of H. incongruens was 1.1 mg metal/L for CuO and 0.36 mg metal/L for ZnO. The addition of algae to D. magna test medium mitigated the toxicity of CuO and ZnO NP 4–11-fold when the test was conducted in natural water but not in the artificial freshwater. The addition of algae mitigated the toxicity of CuSO4 (but not ZnSO4) to D. magna at least 3-fold, whatever the test medium. In the 6-day H. incongruens tests (all exposures included algae), only up to 2-fold differences in metal NP and salt toxicity between mineral and natural test media were observed. To add environmental relevance to NP hazard assessment for the freshwater ecosystem, toxicity tests could be conducted in natural water and organisms could be fed during the exposure.

Chitosan-Stabilized Ag Nanoparticles with Superior Biocompatibility and Their Synergistic Antibacterial Effect in Mixtures with Essential Oils

Silver nanoparticles (AgNPs) are considered a promising alternative to the use of antibiotics in fighting multidrug-resistant pathogens. However, their use in medical application is hindered by the public concern regarding the toxicity of metallic nanoparticles. In this study, rationally designed AgNP were produced, in order to balance the antibacterial activity and toxicity. A facile, environmentally friendly synthesis was used for the electrochemical fabrication of AgNPs. Chitosan was employed as the capping agent, both for the stabilization and to improve the biocompatibility. Size, morphology, composition, capping layer, and stability of the synthesized nanoparticles were characterized. The in vitro biocompatibility and antimicrobial activities of AgNPs against common Gram-negative and Gram-positive bacteria were evaluated. The results revealed that chitosan-stabilized AgNPs were nontoxic to normal fibroblasts, even at high concentrations, compared to bare nanoparticles, while significant antibacterial activity was recorded. The silver colloidal dispersion was further mixed with essential oils (EO) to increase the biological activity. Synergistic effects at some AgNP–EO ratios were observed, as demonstrated by the fractionary inhibitory concentration values. Our results reveal that the synergistic action of both polymer-stabilized AgNPs and essential oils could provide a significant efficiency against a large variety of microorganisms, with minimal side effects.

The effects and the potential mechanism of environmental transformation of metal nanoparticles on their toxicity in organisms

The influence of environmental transformation on the toxicity of metal nanoparticles and possible mechanisms are recapitulated and discussed.

Cerium oxide nanoparticle elicits oxidative stress, endocrine imbalance and lowers sperm characteristics in testes of balb/c mice.

The toxicity of metallic nanoparticles is a growing concern due to its application in industries and homes. We investigated the toxicity of cerium oxide nanoparticles (CeO2 NPs) on reproductive system in male balb/c mice. Twenty mice were divided into four groups of five animals each and treated thus: normal saline (control), 100, 200 and 300μg/kg CeO2 NPs (i.p.,) thrice in a week for five consecutive weeks. Results showed that CeO2 NPs significantly reduced the levels of haemoglobin, PCV and RBC count relative to controls. In addition, luteinising and follicle-stimulating hormones (FSH and LH) and prolactin were significantly reduced in the mice. Specifically, CeO2 NPs at 100μg/kg decreased testosterone by 23%, while CeO2 NPs at 200μg/kg decreased FSH, LH and prolactin by 25%, 26% and 13%, respectively. Testicular malondialdehyde was increased by 103%, 106% and 135% in mice treated with 100, 200 and 300μg/kg CeO2 NPs, respectively. CeO2 NPs caused a significant reduction in activities of antioxidant enzymes and levels of reduced glutathione and total nitric oxide. Moreso, CeO2 NPs decreased sperm motility and count and increased total sperm abnormality in mice. Histology revealed congestion and degeneration of seminiferous tubules. Overall, CeO2 NPs induces testicular dysfunction via disruption of antioxidant/oxidant balance and endocrine suppression.

Impact of counterions on the toxicity of metallic nanoparticles on hepatic cell lines in vitro

Impact of counterions on the toxicity of metallic nanoparticles on hepatic cell lines in vitro

Regulation of apoptosis through bcl-2/bax proteins expression and DNA damage by nano-sized gadolinium oxide.

Gadolinium oxide (Gd2O3) nanoparticles (GNPs) are applied in industrial products, for example, additives, optical glass, and catalysis. There are various suggestions of metal nanoparticles paradigm but the underlying basic mechanism about the toxicity of metal nanoparticles, for example GNPs, remains unclear. This experiment was done to measure the effective toxicity of GNPs (10, 25, 50, and 100 µg/mL) over 24 and 48 h and to evaluate toxicity mechanism in human neuronal (SH-SY5Y) cells. GNPs produced reactive oxygen species (ROS), as evaluated by 2′, 7′-dichlorodihydrofluorescein diacetate. Due to incorporation into cells, GNPs generated ROS in a concentration- and time-dependent manner. To determine the toxicity of GNP mechanism related to ROS, we also found chromosome condensation and dysfunction of mitochondrial membrane potential (MMP) after exposure of GNPs. Furthermore, the increased cell apoptosis rate and DNA fragmentation were closely related to the increased dose and exposure duration of GNPs in SH-SY5Y cells. The reduction in MMP with a simultaneous increase in the expression of bax/bcl2 gene ratio indicated that mitochondria-mediated pathway involved in GNPs induced apoptosis. Thus, our finding has provided valuable insights into the probable mechanism of apoptosis caused by GNPs at in vitro level.

Looking for Biological Protectors against Adverse Health Effects of Some Nanoparticles that Can Pollute Workplace and Ambient Air (A Summary of Authors’ Experimental Results)

Especially high health risks associated with impacts of metallic nanoparticles (Me-NPs) and their presence in the workplace and ambient air of not only the nano-industry but also of some long-existing traditional technologies make it necessary, along with keeping respective dangerous exposures as low as possible, to look for ways of increasing the organism’s resistance to them. Based on theoretical premises of such beneficial interference with toxicokinetics and toxicodynamics of Me-NPs developed by our research team and on understanding general and specific key mechanisms of different Me-NPs’ toxic action, we proposed several bioprotective complexes (BPCs) comprising mainly pectin, some vitamins, glutamate, glycine, N-acetylcysteine, omega-3 PUFA, and different essential trace elements. Results of our animal experiments with different Me-NPs showed that, against the background of such BPCs’ oral administration, the integral and specific toxicity of Me-NPs and even their genotoxicity can be markedly attenuated. Therefore we would recommend to further develop this vector of nano-toxicological research.

Environmental processes and toxicity of metallic nanoparticles in aquatic systems as affected by natural organic matter

The key roles of NOM affecting environmental processes and toxicity of MNPs in aquatic environments are discussed and presented.

Toxicity of metal nanoparticles with a focus on silver

Properties of nanoparticles are significantly different from their bulk counterparts, including their biological and toxic activity. The properties of silver nanoparticles governing their toxicological effects are summarized. These basic characteristics can be used as descriptors for modelling the toxic properties of nanoparticles.