Toxicity assessment of anatase and rutile titanium dioxide nanoparticles: The role of degradation in different pH conditions and light exposure

Titanium dioxide nanoparticles (TiO₂NPs), in the two crystalline forms, rutile and anatase, have been widely used in many industrial fields, especially in cosmetics. Therefore, a lot of details about their safety issues have been discussed by the scientific community. Many studies have led to a general agreement about TiO₂NPs toxicity, in particular for anatase form, but no mechanism details have been proved yet. In this study, data confirm the different toxic potential of rutile and anatase TiO₂NPs in two cell lines up to 5 nM nanoparticles concentration. Moreover, we evaluated the role of titanium ions released by TiO₂NPs in different conditions, at pH = 4.5 (the typical lysosomal compartment pH) and at pH = 5.5 (the skin physiological pH) in conditions of darkness and light, to mimic the dermal exposure of cosmetics. Anatase nanoparticles were proner to degradation both in the acidic conditions and at skin pH. Our study demonstrates that pH and sunlight are dominant factors to induce oxidative stress, TiO₂NPs degradation and toxicity effects.     

The noncellular reduction of MTT tetrazolium salt by TiO2 nanoparticles and its implications for cytotoxicity assays

We report results of noncellular tests, revealing the occurrence of photocatalytic interactions between titanium dioxide (TiO₂, titania) nanoparticles and the MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide] cytotoxicity indicator. These interactions induce the reduction of MTT and formation of purple formazan under biologically relevant conditions. Classical MTT assays have been performed to evaluate the production of formazan in DMEM-F12 and RPMI-1640 cell culture media (containing 10% fetal bovine serum-FBS) treated with Degussa-P25 TiO₂ nanoparticles, in the absence of cells. The colorimetric determinations revealed the noncellular MTT to formazan transformation induced by TiO₂ nanoparticles, under conditions commonly used for in vitro cytotoxicity testing of nanomaterials. The formazan precipitation was found to be proportional to the TiO₂ concentration, being enhanced under laboratory daylight exposure. The photocatalytic nature of the studied effect was assessed under UV irradiation at 365 nm. The biological significance of the reported reaction was established with respect to cellular reference experiments performed on V79-4, HeLa and B16 cell lines. The results show false viability increases with up to 14% (for TiO₂ concentrations generally higher than 50 μg/ml), induced by the TiO₂–MTT reaction. This type of artifacts may lead to underestimated toxicity or false proliferation results.     

Activation of human neutrophils by titanium dioxide (TiO2) nanoparticles

This paper describes the in vitro effects of titanium dioxide (TiO₂) nanoparticles (NPs) upon human neutrophils. Kinetic experiments revealed no cell necrosis after 24 h of treatment with TiO₂ (0–100 μg/ml). In contrast, TiO₂-induced change in cellular morphology in a concentration-dependent manner in neutrophils over time, indicating its potential to activate these cells. To further support this, we demonstrated that TiO₂ markedly and rapidly induced tyrosine phosphorylation events, including phosphorylation of two key enzymes, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases-1/2 (Erk-1/2). We also determined the effects of TiO₂ on two neutrophil functions requiring a longer exposure period between NPs and cells: apoptosis and cytokine production. Interestingly, at concentrations ⩾20 μg/ml, TiO₂ inhibited neutrophil apoptosis in a concentration-dependent manner after 24 h of treatment. Supernatants from TiO₂-induced neutrophils were harvested after 24 h and tested for the presence of 36 different analytes (cytokines, chemokines) using an antibody array assay. TiO₂ treatment increased production of 13 (36%) analytes, including IL-8, which exhibited the greatest increase (∼16 × control cell levels). The increased production of IL-8 was confirmed by ELISA. We conclude that TiO₂ exerts important neutrophil agonistic properties in vitro.     

Maternal exposure to titanium dioxide nanoparticles during pregnancy; impaired memory and decreased hippocampal cell proliferation in rat offspring

Titanium dioxide nanoparticles (TiO₂-NPs) are massively produced in the environment, and because of their wide usage, they are a potential risk of damage to human health. TiO₂-NPs are often used as additives for paints, papers, and foods. The central nervous system (CNS), including hippocampal regions, is potentially susceptible targets for TiO₂-NPs. This study aimed to determine the effects of exposure to TiO₂-NPs during pregnancy on hippocampal cell proliferation and the learning and memory of offspring. Pregnant Wistar rats received intragastric TiO₂-NPs (100 mg/kg body weight) daily from gestational day (GD) 2 to (GD) 21. Animals in the control group received the same volume of distilled water via gavage. After delivery, the one-day-old neonates were deeply anesthetized and weighed. They were then killed and the brains of each group were collected. Sections of the brains from the rat offspring were stained using Ki-67 immunolabeling and the immunohistochemistry technique. Some of the male offspring (n = 12 for each group) were weaned at postnatal day (PND21), and housed until adulthood (PND60). Then the learning and memory in animals of each group were evaluated using passive avoidance and Morris water maze tests. The immunolabeling of Ki-67 protein as a proliferating cell marker showed that TiO₂-NPs significantly reduced cell proliferation in the hippocampus of the offspring (P < 0.05). Moreover, both the Morris water maze test and the passive avoidance test showed that exposure to TiO₂-NPs significantly impaired learning and memory in offspring (P < 0.05). These results may provide basic experimental evidence for a better understanding of the neurotoxic effects of TiO₂-NPs on neonatal and adult brains.     

Influence of silver and titanium dioxide nanoparticles on in vitro blood-brain barrier permeability

An in vitro blood-brain barrier (BBB) model being composed of co-culture with endothelial (bEnd.3) and astrocyte-like (ALT) cells was established to evaluate the toxicity and permeability of Ag nanoparticles (AgNPs; 8 nm) and TiO₂ nanoparticles (TiO₂NPs; 6 nm and 35 nm) in normal and inflammatory central nervous system. Lipopolysaccharide (LPS) was pre-treated to simulate the inflammatory responses. Both AgNPs and Ag ions can decrease transendothelial electrical resistance (TEER) value, and cause discontinuous tight junction proteins (claudin-5 and zonula occludens-1) of BBB. However, only the Ag ions induced inflammatory cytokines to release, and had less cell-to-cell permeability than AgNPs, which indicated that the toxicity of AgNPs was distinct from Ag ions. LPS itself disrupted BBB, while co-treatment with AgNPs and LPS dramatically enhanced the disruption and permeability coefficient. On the other hand, TiO₂NPs exposure increased BBB penetration by size, and disrupted tight junction proteins without size dependence, and many of TiO₂NPs accumulated in the endothelial cells were observed. This study provided the new insight of toxic potency of AgNPs and TiO₂NPs in BBB.     

Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay: A quantitative method for oxidative stress assessment of nanoparticle-treated cells

No consensus exists on how to address possible toxicity of nanomaterials as they interfere with most in vitro screening tests based on colorimetric and fluorimetric probes such as the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay for detection of oxidative species.In the present research, nanomaterial interaction with DCFH-DA was studied in relation to its nature and/or assay conditions (cell-based and time exposure) by incubating Rhodamine (Rhd)-labeled 25 nm and 50 nm silica (SiO₂), naked and oleic acid coated magnetite, (Fe₃O₄) and maghemite (Fe₂O₃) iron oxide, titanium dioxide (TiO₂) and poly(ethylene oxide)-poly(lactide/glycolide) acid (PLGA-PEO) nanoparticles (NPs) with metabolically active rat hepatocytes for 4 and 24-h periods. Data indicated that nanoparticle uptake correlated with quenching of dye fluorescence emission. In spite of their masking effect, the oxidative potential of NPs could be detected at a limited threshold concentration when exposed for periods of time longer than those frequently used for this test. However, changes in the experimental conditions did not systematically result in free radical formation for all nanomaterials tested.Overall data indicate that despite the quenching effect of nanoparticles on DCFH-DA assay, it can be considered as a useful tool for quantitative measurement of NPs-induced oxidative stress by minor modifications of standardized protocols.     

Effects of TiO2 nanoparticles on ROS production and growth inhibition using freshwater green algae pre-exposed to UV irradiation

This study investigated the possibility that titanium dioxide nanoparticles (nano-TiO₂) toxicity in Pseudokirchneriella subcapitata involves reactive oxygen species (ROS) production, using the dichlorodihydrofluorescein (DCF) assay. Algae were exposed to nano-TiO₂ under laboratory fluorescent lamps supplemented with UV irradiation for 3 h, with or without a UV filter. Results showed that nano-TiO₂ increased ROS production in UV-exposed cells, with or without a UV filter (LOEC values were 250 and 10 mg/L, respectively). Sublethal effects of nano-TiO₂ on UV pre-exposed algae were also examined. Toxicity studies indicated that exposure to nano-TiO₂ agglomerates decreased algal growth following 3 h pre-exposure to UV, with or without a UV filter (EC₅₀s were 8.7 and 6.3 mg/L, respectively). The present study suggests that the growth inhibitory effects of nano-TiO₂ in algae occurred at concentrations lower than those that can elevate DCF fluorescence, and that ROS generation is not directly involved with the sublethal effects of nano-TiO₂ in algae.     

Toxicity and accumulation of Copper oxide (CuO) nanoparticles in different life stages of Artemia salina

Metal nanoparticles production rate and its applications have raised concerns about their release and toxicity to the aquatic and terrestrial organisms. The primary size of Copper Oxide nanoparticles (CuO NP’s) was found to be 114 ± 36 nm using Scanning Electron Microscopy (SEM) and a significant increase in the hydrodynamic diameter of CuO NP was seen within 1 h of interaction. The median lethal concentration (LC₅₀) values obtained from the acute toxicity studies on different life stages of Artemia salina was found to be 61.4, 35, 12.2 and 175.2 mg/L for 1d, 2d, 7d old and adult, respectively. The toxicity associated changes in biochemical markers such as Catalase, Reduced glutathione and Glutathione-S-Transferase were evident. The accumulation of Cu nanoparticles into the gut of Artemia salina was the major reason for toxicity. This study demonstrate the toxicity of CuO NPs to Artemia salina, and the obtained results necessitate the detailed investigation on the possible eco-toxicological implication of these nanomaterials.     

TiO2 nanoparticles induce endothelial cell activation in a pneumocyte–endothelial co-culture model

The effects of particulate matter (PM) on endothelial cells have been evaluated in vitro by exposing isolated endothelial cells to different types of PM. Although some of the findings from these experiments have been corroborated by in vivo studies, an in vitro model that assesses the interaction among different cell types is necessary to achieve more realistic assays. We developed an in vitro model that mimics the alveolar–capillary interface, and we challenged the model using TiO₂ nanoparticles (TiO₂-NPs). Human umbilical endothelial cells (HUVECs) were cultured on the basolateral side of a membrane and pneumocytes (A549) on the apical side. Confluent co-cultures were exposed on the apical side to 10 μg/cm² of TiO₂-NPs or 10 ng/mL of TNFα for 24 h. Unexposed cultures were used as negative controls. We evaluated monocyte adhesion to HUVECs, adhesion molecule expression, nitric oxide concentration and proinflammatory cytokine release. The TiO₂-NPs added to the pneumocytes induced a 3- to 4-fold increase in monocyte adhesion to the HUVECs and significant increases in the expression of adhesion molecules (4-fold for P-selectin at 8 h, and about 8- and 10-fold for E-selectin, ICAM-1, VCAM-1 and PECAM-1 at 24 h). Nitric oxide production also increased significantly (2-fold). These results indicate that exposing pneumocytes to TiO₂-NPs causes endothelial cell activation.     

The in vivo underlying mechanism for recovery response formation in nano-titanium dioxide exposed Caenorhabditis elegans after transfer to the normal condition

So far, we still know little about mechanism for recovery response of engineered nanomaterials (ENMs). Here we used Caenorhabditis elegans to investigate recovery responses of titanium dioxide nanoparticles (TiO₂-NPs) exposed animals and the underlying mechanism. After acute exposure to TiO₂-NPs (100 mg/L), endpoints including defecation and permeable state of intestinal barrier of exposed nematodes returned to control levels; however, after prolonged exposure to TiO₂-NPs (100 μg/L), endpoints of exposed nematodes could not be recovered to control levels under the normal condition. After prolonged exposure to TiO₂-NPs, nematodes exhibited severe deficits in development of intestinal barrier and AVL and DVB neurons controlling defecation; however, after acute exposure to TiO₂-NPs, nematodes had normal developmental state of intestinal barrier and AVL and DVB neurons. Our results imply that developmental states of intestinal barrier and AVL and DVB neurons may serve as a pivotal determinant for recovery response in TiO₂-NPs exposed nematodes.From the Clinical EditorThis basic science study investigates the recovery response to TiO₂ nanoparticles in a nematode model, and concludes that developmental states of the intestinal barrier and AVL and DVB neurons likely serve as determinants for recovery following TiO2-NP exposure.     

TiO2 nanoparticles and bulk material stimulate human peripheral blood mononuclear cells

Nanomaterials are increasingly produced and used throughout recent years. Consequently the probability of exposure to nanoparticles has risen. Because of their small 1–100 nm size, the physicochemical properties of nanomaterials may differ from standard bulk materials and may pose a threat to human health. Only little is known about the effects of nanoparticles on the human immune system. In this study, we investigated the effects of TiO₂ nanoparticles and bulk material in the in vitro model of human peripheral blood mononuclear cells (PBMC) and cytokine-induced neopterin formation and tryptophan breakdown was monitored. Both biochemical processes are closely related to the course of diseases like infections, atherogenesis and neurodegeneration. OCTi60 (25 nm diameter) TiO₂ nanoparticles and bulk material increased neopterin production in unstimulated PBMC and stimulated cells significantly, the effects were stronger for OCTi60 compared to bulk material, while P25 TiO₂ (25 nm diameter) nanoparticles had only little influence. No effect of TiO₂ nanoparticles on tryptophan breakdown was detected in unstimulated cells, whereas in stimulated cells, IDO activity and IFN-γ production were suppressed but only at the highest concentrations tested. Because neopterin was stimulated and tryptophan breakdown was suppressed in parallel, data suggests that the total effect of particles would be strongly pro-inflammatory.     

Spray freeze drying for dry powder inhalation of nanoparticles

Formulating nanoparticles for delivery to the deep lung is complex and many techniques fail in terms of nanoparticle stability. Spray freeze drying (SFD) is suggested here for the production of inhalable nanocomposite microcarriers (NCM). Different nanostructures were prepared and characterized including polymeric and lipid nanoparticles. Nanoparticle suspensions were co-sprayed with a suitable cryoprotectant into a cooled, stainless steel spray tower, followed by freeze drying to form a dry powder while equivalent compositions were spray dried (SD) as controls. SFD-NCM possess larger specific surface areas (67–77 m²/g) and lower densities (0.02 g/cm³) than their corresponding SD-NCM. With the exception of NCM of lipid based nanocarriers, SFD produced NCM with a mass median aerodynamic diameter (MMAD) of 3.0 ± 0.5 μm and fine particle fraction (FPF ⩽ 5.2 μm) of 45 ± 1.6% with aerodynamic performances similar to SD-NCM. However, SFD was superior to SD in terms of maintaining the particle size of all the investigated polymeric and lipid nanocarriers following reconstitution (S_f/S_i ratio for SFD ≈ 1 versus >1.5 for SD). The SFD into cooled air proved to be an efficient technique to prepare NCM for pulmonary delivery while maintaining the stability of the nanoparticles.     

Impact of iron oxide nanoparticles on brain,heart, lung,liver and kidneys mitochondrial respiratory chain complexes activities and coupling

The present study evaluates the effects of iron oxide nanoparticles (ION) on mitochondrial respiratory chain complexes activities in five organs characterized by different oxidative capacities and strongly involved in body detoxification. Isolated mitochondria were extracted from brain, heart, lung, liver and kidneys in twelve Wistar rats (8 weeks) using differential centrifugations. Maximal oxidative capacities (Vmax), mitochondrial respiratory chain complexes activity using succinate (Vsucc, complexes II, III, and IV activities) or N, N, N′, N′-tetramethyl-p-phenylenediaminedihydrochloride (tmpd)/ascorbate (Vtmpd, complex IV activity) and, mitochondrial coupling (Vmax/Vo) were determined in controls and after exposure to 100, 200, 300 and 500 μg/ml Fe₃O₄. Data showed that baseline maximal oxidative capacities were 26.3 ± 4.7, 48.9 ± 4.6, 11.3 ± 1.3, 27.0 ± 2.5 and 13.4 ± 1.7 μmol O₂/min/g protein in brain, heart, lung, liver, and kidneys mitochondria, respectively. Complexes II, III, and IV activities also significantly differed between the five organs. Interestingly, as compared to baseline values and in all tissues examined, exposure to ION did not alter mitochondrial respiratory chain complexes activities whatever the nanoparticles (NPs) concentration used. Thus, ION did not show any toxicity on mitochondrial coupling and respiratory chain complexes I, II, III, and IV activities in these five major organs.     

Effects of TiO2 nanoparticles at predicted environmental relevant concentration on the marine scallop Chlamys farreri: An integrated biomarker approach

Manufactured nanoparticles (NPs) have caused extensive concern about their toxic effects on the marine environment. However, the chronic toxicity of NPs at predicted environmental relevant concentration on the marine organisms is poorly understood. In this study, we investigated the oxidative stress, neurotoxicity and histopathological effects of TiO₂ NPs at predicted environmental relevant concentration (1 mg/L) to marine scallop Chlamys farreri. The results showed that TiO₂ NPs caused obviously oxidative damage on the scallops as evidenced by the significantly elevated superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) contents. The increased acetylcholine esterase (AChE) activities reflected neurotoxicity of TiO₂ NPs. The histopathological analysis revealed alterations in the gill and digestive gland, such as dysplastic and necrosis. Additionally, integrated biomarker response (IBR) values indicated that TiO₂ NPs can cause strong toxic effects on the scallop. These results suggested that predicted environmental relevant TiO₂ NPs can cause adverse effects on scallops and IBR analysis can be used as an effective approach for risk assessment of NPs on the marine organisms.     

Oxidative stress contributes to silica nanoparticle-induced cytotoxicity in human embryonic kidney cells

In order to elucidate the nanoparticle-induced cytotoxicity and its mechanism, the effects of 20 and 50 nm silica nanoparticles on cultured human embryonic kidney (HEK293) cells were investigated. Cell viability, mitochondrial function, cell morphology, reactive oxygen species (ROS), glutathione (GSH), thiobarbituric acid reactive substance (TBARS), cell cycle and apoptosis were assessed under control and silica exposed conditions. Exposure to 20 or 50 nm SiO₂ nanoparticles at dosage levels between 20 and 100 μg/ml decreased cell viability in a dose-dependent manner. Median lethal dose (LD₅₀) of 24 h exposure was 80.2 ± 6.4 and 140.3 ± 8.6 μg/ml for 20 and 50 nm SiO₂ nanoparticles, respectively. Morphological examination revealed cell shrinkage and nuclear condensation after SiO₂ nanoparticle exposure. Increase in intracellular ROS level and reduction in GSH content were also observed in SiO₂ nanoparticle-exposed HEK293 cells. Increase in the amount of TBARS suggested an elevated level of lipid peroxidation. Flow cytometric analysis showed that SiO₂ nanoparticles can cause G2/M phase arrest and apoptotic sub-G1 population increase in a dose-dependent manner. In summary, exposure to SiO₂ nanoparticles resulted in a dose-dependent cytotoxicity in cultured HEK293 cells that was associated with increased oxidative stress.     

FTIR study of the effect of nTiO2 on the biochemical constituents of gill tissues of Zebrafish (Danio rerio)

In the present study, an attempt is made to assess the changes in the biochemical contents in general, and the protein structural changes in particular, in the gill tissues of Zebrafish (Danio rerio) due to titanium nanoparticles and their bulk counterpart using FTIR spectroscopy. The FTIR spectra show that the intensity differences between the control and titanium-exposed tissues are remarkable. For example, TiO₂-exposed tissues show higher intensities at amide I and amide II of proteins, but lower at 2924 cm^?1 (CH₂ asymmetric stretching of lipids), 2853 cm^?1 (CH₂ symmetric stretching of lipids) and 1744 cm^?1 (CO stretching of phospholipids) when compared with the control tissues. This suggests that there is an increase or decrease in the percentage of a certain types of biomolecules relative to the total infrared-active constituents in the gill tissues. The curve-fitting analysis suggests an increase in α-helical structure and a decrease in β-sheet structure due to TiO₂ exposure. These results confirm that the structural conformation of proteins in fish gill tissues was significantly influenced by TiO₂ exposure. Further, the changes are more due to nTiO₂ when compared to TiO₂ bulk, suggesting that nTiO₂ are affecting the biochemical constituents more than their bulk counterpart.     

Profiling of the toxicity mechanisms of coated and uncoated silver nanoparticles to yeast Saccharomyces cerevisiae BY4741 using a set of its 9 single-gene deletion mutants defective in oxidative stress response,cell wall or membrane integrity and endocytosis

The widespread use of nanosilver in various antibacterial, antifungal, and antiviral products warrants the studies of the toxicity pathways of nanosilver-enabled materials toward microbes and viruses. We profiled the toxicity mechanisms of uncoated, casein-coated, and polyvinylpyrrolidone-coated silver nanoparticles (AgNPs) using Saccharomyces cerevisiae wild-type (wt) and its 9 single-gene deletion mutants defective in oxidative stress (OS) defense, cell wall/membrane integrity, and endocytosis. The 48-h growth inhibition assay in organic-rich growth medium and 24-h cell viability assay in deionized (DI) water were applied whereas AgNO₃, H₂O_2, and SDS served as positive controls. Both coated AgNPs (primary size 8–12 nm) were significantly more toxic than the uncoated (~ 85 nm) AgNPs. All studied AgNPs were ~ 30 times more toxic if exposed to yeast cells in DI water than in the rich growth medium: the IC₅₀ based on nominal concentration of AgNPs in the growth inhibition test ranged from 77 to 576 mg Ag/L and in the cell viability test from 2.7 to 18.7 mg Ag/L, respectively. Confocal microscopy showed that wt but not endocytosis mutant (end3Δ) internalized AgNPs. Comparison of toxicity patterns of wt and mutant strains defective in OS defense and membrane integrity revealed that the toxicity of the studied AgNPs to S. cerevisiae was not caused by the OS or cell wall/membrane permeabilization.     

Darunavir/ritonavir and raltegravir coadministered in routine clinical practice: Potential role for an unexpected drug interaction

The present study aimed to investigate potential drug interactions between darunavir and raltegravir in patients treated for HIV infection. We enrolled HIV-infected subjects on darunavir-containing regimens that underwent measurement of plasma darunavir trough concentration (12 ± 3 h after dosing). Two groups of patients were compared: those taking darunavir plus a nucleoside/nucleotide backbone (group 1) or a backbone + raltegravir (group 2). Interindividual pharmacokinetic variability was evaluated through the coefficient of variation (CV_inter).We obtained 156 plasma samples from 63 patients, of which 44 in group 1 and 19 in group 2. Overall, darunavir geometric mean concentration was 2.90 mg/L (95% CI 2.34–3.60) while ritonavir geometric mean concentration was 0.21 mg/L (95% CI 0.17–0.27). We observed a high inter-individual variability in darunavir (CV_inter 59%) and ritonavir (CV_inter 103%) plasma levels. Darunavir concentration correlated with concomitant ritonavir levels (r = 0.476, p < 0.001). Patients in group 1 had a higher darunavir geometric mean concentration than those in group 2 [3.44 mg/L (95% CI 2.79–4.23) versus 1.95 mg/L (95% CI 1.19–3.20), p = 0.017]. However, the proportion of subjects with concomitant HIV-RNA <50 copies/mL was higher in group 2 (78.9% versus 47.7%, p = 0.028). In a multivariable model, raltegravir co-administration was independently related to a lower darunavir concentration (mean difference ?0.25 log₁₀ mg/L, 95% CI ?0.46/?0.04, p = 0.020) after adjusting for time from last drug intake and concomitant drugs used.In conclusion, a potential drug interaction between darunavir and raltegravir was observed, although this did not seem virologically significant. For the distinct metabolic pathways of these drugs, its mechanism remains to be determined.     

Nano-based antileishmanial agents: A toxicological study on nanoparticles for future treatment of cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) is endemic in the tropical and subtropical countries. Antileishmanial drugs that are traditionally used for treatment of CL are mainly toxic, ineffective for some parasite isolates, and mostly expensive. Previous studies showed that some metal and metal oxide nanoparticles have antimicrobial activity. Moreover, the use of nanoparticles together with ultra violet (UV) and infra red (IR) light increases toxic effects of nanoparticles by generation of reactive oxygen species (ROSs) and heat, respectively. There is little information on antileishmanial activity of nanoparticles, alone or together with UV/IR. Thus, the purpose of this research was to study antileishmanial effects of some nanoparticles including silver nanoparticles (Ag NPs), gold nanoparticles (Au NPs), titanium dioxide nanoparticles (TiO₂ NPs), zinc oxide nanoparticles (ZnO NPs), and magnesium oxide nanoparticles (MgO NPs) on Leishmania major parasites under UV, IR, and dark conditions. After 24 h exposure to nanoparticles, different biological parameters such as cell viability, proliferation, infectivity, and infection index were investigated under UV/IR/dark conditions. In this study, the highest antileishmanial activity was seen for Ag NPs, followed by Au NPs, TiO₂ NPs, ZnO NPs, and MgO NPs. Both UV and IR light increased antileishmanial properties of all nanoparticles. In spite of antileishmanial activity of nanoparticles under UV, IR, and dark conditions, these nanoparticles had high cytotoxicity on macrophages, which must be considered in future studies. The authors declare that the use of nanoparticles for treatment of CL may have both positive and negative consequences.