The Amoebicidal Activity of Diferrocenyl Derivatives: A Significant Dependence on the Electronic Environment.

Amoebiasis is the second leading cause of death worldwide associated with parasitic disease and is becoming a critical health problem in low-income countries, urging new treatment alternatives. One of the most promising strategies is enhancing the redox imbalance within these susceptible parasites related to their limited antioxidant defense system. Metal-based drugs represent a perfect option due to their extraordinary capacity to stabilize different oxidation states and adopt diverse geometries, allowing their interaction with several molecular targets. This work describes the amoebicidal activity of five 2-(Z-2,3-diferrocenylvinyl)-4X-4,5-dihydrooxazole derivatives (X = H (3a), Me (3b), iPr (3c), Ph (3d), and benzyl (3e)) on Entamoeba histolytica trophozoites and the physicochemical, experimental, and theoretical properties that can be used to describe the antiproliferative activity. The growth inhibition capacity of these organometallic compounds is strongly related to a fine balance between the compounds' redox potential and hydrophilic character. The antiproliferative activity of diferrocenyl derivatives studied herein could be described either with the redox potential, the energy of electronic transitions, logP, or the calculated HOMO-LUMO values. Compound 3d presents the highest antiproliferative activity of the series with an IC50 of 23 µM. However, the results of this work provide a pipeline to improve the amoebicidal activity of these compounds through the directed modification of their electronic environment.

A Comparative Study of Cancer Cells Susceptibility to Silver Nanoparticles Produced by Electron Beam.

INTRODUCTION: Silver nanoparticles (AgNPs) have a wide range of bioactivity, which is highly dependent on particle size, shape, stabilizer, and production method. Here, we present the results of studies of AgNPs cytotoxic properties obtained by irradiation treatment of silver nitrate solution and various stabilizers by accelerating electron beam in a liquid medium. METHODS: The results of studies of morphological characteristics of silver nanoparticles were obtained by transmission electron microscopy, UV-vis spectroscopy, and dynamic light scattering measurements. MTT test, alamar blue test, flow cytometry, and fluorescence microscopy were used to study the anti-cancer properties. As biological objects for standard tests, adhesive and suspension cell cultures of normal and tumor origin, including prostate cancer, ovarian cancer, breast cancer, colon cancer, neuroblastoma, and leukemia, were studied. RESULTS: The results showed that the silver nanoparticles obtained by irradiation with polyvinylpyrrolidone and collagen hydrolysate are stable in solutions. Samples with different stabilizers were characterized by a wide average size distribution from 2 to 50 nm and low zeta potential from -7.3 to +12.4 mV. All AgNPs formulations showed a dose-dependent cytotoxic effect on tumor cells. It has been established that the particles obtained with the combination of polyvinylpyrrolidone/collagen hydrolysate have a relatively more pronounced cytotoxic effect in comparison to samples stabilized with only collagen or only polyvinylpyrrolidone. The minimum inhibitory concentrations for nanoparticles were less than 1 µg/mL for various types of tumor cells. It was found that neuroblastoma (SH-SY5Y) is the most susceptible, and ovarian cancer (SKOV-3) is the most resistant to the action of silver nanoparticles. The activity of the AgNPs formulation prepared with a mixture of PVP and PH studied in this work was higher that activity of other AgNPs formulations reported in the literature by about 50 times. CONCLUSIONS: The results indicate that the AgNPs formulations synthesized with an electron beam and stabilized with polyvinylpyrrolidone and protein hydrolysate deserve deep study for their further use in selective cancer treatment without harming healthy cells in the patient organism.

Antiproliferative Effect of Essential Oil Obtained from Oregano (Lippia palmeri S. Watson) Leaves Grown in Hydroponics and LED Light.

Nowadays, light-emitting diodes (LED) provide an alternative source to sunlight with specific intensity and wavelength that promotes plant growth. The features offered by LED could also stimulate the production of secondary metabolites of pharmaceutical interest. This work analyzed the cultivation of oregano (Lippia palmeri S. Watson) in a floating root hydroponic system supplemented by full-spectrum LED artificial light. Growth indicators like height, diameter, number of shoots, and leaf length and width were measured. The essential oil (EO) composition from the leaves of wild and hydroponic conditions found thymol (41.8 %) as the main product for the former and carvacrol (47 %) in hydroponics. The antiproliferative activity of EOs on human colorectal cancer HCT-15 shows that 6.4 µg/ml for hydroponic and 7.4 µg/ml for the wild plant reduce more than 50 % the cell viability. Overall, this study indicates that hydroponic conditions and full spectrum LED modifies the composition of the EO of L. palmeri on compared with the wild plant, which effectively induces cell growth inhibition in human colorectal cancer.

Lung Models to Evaluate Silver Nanoparticles' Toxicity and Their Impact on Human Health.

Nanomaterials (NMs) solve specific problems with remarkable results in several industrial and scientific areas. Among NMs, silver nanoparticles (AgNPs) have been extensively employed as drug carriers, medical diagnostics, energy harvesting devices, sensors, lubricants, and bioremediation. Notably, they have shown excellent antimicrobial, anticancer, and antiviral properties in the biomedical field. The literature analysis shows a selective cytotoxic effect on cancer cells compared to healthy cells, making its potential application in cancer treatment evident, increasing the need to study the potential risk of their use to environmental and human health. A large battery of toxicity models, both in vitro and in vivo, have been established to predict the harmful effects of incorporating AgNPs in these numerous areas or those produced due to involuntary exposure. However, these models often report contradictory results due to their lack of standardization, generating controversy and slowing the advances in nanotoxicology research, fundamentally by generalizing the biological response produced by the AgNP formulations. This review summarizes the last ten years' reports concerning AgNPs' toxicity in cellular respiratory system models (e.g., mono-culture models, co-cultures, 3D cultures, ex vivo and in vivo). In turn, more complex cellular models represent in a better way the physical and chemical barriers of the body; however, results should be used carefully so as not to be misleading. The main objective of this work is to highlight current models with the highest physiological relevance, identifying the opportunity areas of lung nanotoxicology and contributing to the establishment and strengthening of specific regulations regarding health and the environment.

Bell Shape Curves of Hemolysis Induced by Silver Nanoparticles: Review and Experimental Assay.

The hemolytic activity assay is a versatile tool for fast primary toxicity studies. This work presents a systematic study of the hemolytic properties of ArgovitTM silver nanoparticles (AgNPs) extensively studied for biomedical applications. The results revealed an unusual and unexpected bell-shaped hemolysis curve for human healthy and diabetic donor erythrocytes. With the decrease of pH from 7.4 and 6.8 to 5.6, the hemolysis profiles for AgNPs and AgNO3 changed dramatically. For AgNPs, the bell shape changed to a step shape with a subsequent sharp increase, and for AgNO3 it changed to a gradual increase. Explanations of these changes based on the aggregation of AgNPs due to the increase of proton concentration were suggested. Hemolysis of diabetic donor erythrocytes was slightly higher than that of healthy donor erythrocytes. The meta-analysis revealed that for only one AgNPs formulation (out of 48), a bell-shaped hemolysis profile was reported, but not discussed. This scarcity of data was explained by the dominant goal of studies consisting in achieving clinically significant hemolysis of 5-10%. Considering that hemolysis profiles may be bell-shaped, it is recommended to avoid extrapolations and to perform measurements in a wide concentration interval in hemolysis assays.

Toxicological Evaluations in Macrophages and Mice Acutely and Chronically Exposed to Halloysite Clay Nanotubes Functionalized with Polystyrene.

Halloysite clay nanotubes (HNTs) have been proposed as highly biocompatible for several biomedical applications. Various polymers have been used to functionalize HNTs, but scarce information exists about polystyrene for this purpose. This work evaluated polystyrene-functionalized HNTs (FHNTs) by comparing its effects with non-FHNTs and innocuous talc powder on in vitro and in vivo models. Monocyte-derived human or murine macrophages and the RAW 264.7 cell line were treated with 0.01, 0.1, 1, and 100 µg mL-1 FHNTs, HNTs, or talc to evaluate the cytotoxic and cytokine response. Our results show that nanoclays did not cause cytotoxic damage to macrophages. Only the 100 µg mL-1 concentration induced slight proinflammatory cytokine production at short exposure, followed by an anti-inflammatory response that increases over time. CD1 mice treated with a single dose of 1, 2.5, or 5 mg Kg-1 of FHNTs or HNTs by oral and inhalation routes caused aluminum accumulation in the kidneys and lungs, without bodily signs of distress or histopathological changes in any treated mice, evaluated at 48 h and 30 days post-treatment. Nanoclay administration simultaneously by four different parenteral routes (20 mg Kg-1) or the combination of administration routes (parenteral + oral or parenteral + inhalation; 25 mg Kg-1) showed accumulation on the injection site and slight surrounding inflammation 30 days post-treatment. CD1 mice chronically exposed to HNTs or FHNTs in the bedding material (ca 1 mg) throughout the parental generation and two successive inbred generations for 8 months did not cause any inflammatory process or damage to the abdominal organs and the reproductive system of the mice of any of the generations, did not affect the number of newborn mice and their survival, and did not induce congenital malformations in the offspring. FHNTs showed a slightly less effect than HNTs in all experiments, suggesting that functionalization makes them less cytotoxic. Doses of up to 25 mg Kg-1 by different administration routes and permanent exposure to 1 mg of HNTs or FHNTs for 8 months seem safe for CD1 mice. Our in vivo and in vitro results indicate that nanoclays are highly biocompatible, supporting their possible safe use for future biomedical and general-purpose applications.

Treatment with Argovit® Silver Nanoparticles Induces Differentiated Postharvest Biosynthesis of Compounds with Pharmaceutical Interest in Carrot (Daucus carota L.).

The global market for plant-derived bioactive compounds is growing significantly. The use of plant secondary metabolites has been reported to be used for the prevention of chronic diseases. Silver nanoparticles were used to analyze the content of enhancement phenolic compounds in carrots. Carrot samples were immersed in different concentrations (0, 5, 10, 20, or 40 mg/L) of each of five types of silver nanoparticles (AgNPs) for 3 min. Spectrophotometric methods measured the total phenolic compounds and the antioxidant capacity. The individual phenolic compounds were quantified by High Performance Liquid Chromatography (HPLC) and identified by -mass spectrometry (HPLC-MS). The five types of AgNPs could significantly increase the antioxidant capacity of carrots' tissue in a dose-dependent manner. An amount of 20 mg/L of type 2 and 5 silver nanoparticle formulations increased the antioxidant capacity 3.3-fold and 4.1-fold, respectively. The phenolic compounds that significantly increased their content after the AgNP treatment were chlorogenic acid, 3-O-caffeoylquinic acid, and 5'-caffeoylquinic acid. The increment of each compound depended on the dose and the type of the used AgNPs. The exogenous application of Argovit® AgNPs works like controlled abiotic stress and produces high-value secondary bioactive compounds in carrot.

The Infectious Bronchitis Coronavirus Pneumonia Model Presenting a Novel Insight for the SARS-CoV-2 Dissemination Route.

Infectious bronchitis (IB) of chickens is a highly contagious disease characterized by damage of the respiratory system and reproductive organs in young animals caused by a virus of the genus Gamma coronavirus. The condition of the respiratory system caused by the IB virus in chickens has many similarities with the pathology of the respiratory system caused by SARS-CoV-2 in humans. The effectiveness of virucidal drugs (Argovit, Triviron, Ecocid, and lauric acid monoglyceride) was tested on chickens inoculated with a tenfold dose of a vaccine strain based on the attenuated virus H120 against IB of chickens. On the 6th day after inoculation, inflammatory changes in the intestines, lungs, and thymus were observed in the control group. The experimental groups were characterized by less pronounced inflammatory reactions and a lower proportion of thymus and lung probes containing genomic IB virus RNA. Since the virucidal activity of four orally administrated formulations was possible only in the intestine, the experimental data indirectly confirmed the hypothesis of the possibility of the predominant accumulation of coronaviruses in the intestine and subsequent lung damage due to the hematogenous redistribution of viral particles and IBV antigens. It was suggested that other coronaviruses including SARS-CoV-2 can implement a similar mechanism.

Antitumor Activity against Human Colorectal Adenocarcinoma of Silver Nanoparticles: Influence of [Ag]/[PVP] Ratio.

Silver nanoparticles (AgNPs) not only have shown remarkable results as antimicrobial and antiviral agents but also as antitumor agents. This work reports the complete characterization of five polyvinylpyrrolidone-coated AgNP (PVP-AgNP) formulations, their cytotoxic activity against human colon tumor cells (HCT-15), their cytotoxic effect on primary mouse cultures, and their lethal dose on BALB/c mice. The evaluated AgNP formulations have a composition within the ranges Ag: 1.14-1.32% w/w, PVP: 19.6-24.5% and H2O: 74.2-79.2% with predominant spherical shape within an average size range of 16-30 nm according to transmission electron microscopy (TEM). All formulations assessed increase mitochondrial ROS concentration and induce apoptosis as the leading death pathway on HCT-15 cells. Except for AgNP1, the growth inhibition potency of AgNP formulations of human colon tumor cancer cells (HCT-15) is 34.5 times higher than carboplatin, one of the first-line chemotherapy agents. Nevertheless, 5-10% of necrotic events, even at the lower concentration evaluated, were observed. The cytotoxic selectivity was confirmed by evaluating the cytotoxic effect on aorta, spleen, heart, liver, and kidney primary cultures from BALB/c mice. Despite the cytotoxic effects observed in vitro, the lethal dose and histopathological analysis showed the low toxicity of these formulations (all of them on Category 4 of the Globally Harmonized System of Classification and Labelling of Chemicals) and minor damage observed on analyzed organs. The results provide an additional example of the rational design of safety nanomaterials with antitumor potency and urge further experiments to complete the preclinical studies for these AgNP formulations.

AgNPs Argovit™ Modulates Cyclophosphamide-Induced Genotoxicity on Peripheral Blood Erythrocytes In Vivo.

Silver nanoparticles (AgNPs) have been studied worldwide for their potential biomedical applications. Specifically, they are proposed as a novel alternative for cancer treatment. However, the determination of their cytotoxic and genotoxic effects continues to limit their application. The commercially available silver nanoparticle Argovit™ has shown antineoplastic, antiviral, antibacterial, and tissue regenerative properties, activities triggered by its capacity to promote the overproduction of reactive oxygen species (ROS). Therefore, in this work, we evaluated the genotoxic and cytotoxic potential of the Argovit™ formulation (average size: 35 nm) on BALB/c mice using the micronucleus in a peripheral blood erythrocytes model. Besides, we evaluated the capability of AgNPs to modulate the genotoxic effect induced by cyclophosphamide (CP) after the administration of the oncologic agent. To achieve this, 5-6-week-old male mice with a mean weight of 20.11 ± 2.38 g were treated with water as negative control (Group 1), an single intraperitoneal dose of CP (50 mg/kg of body weight, Group 2), a daily oral dose of AgNPs (6 mg/kg of weight, Group 3) for three consecutive days, or a combination of these treatment schemes: one day of CP doses (50 mg/kg of body weight) followed by three doses of AgNPs (one dose per day, Group 4) and three alternate doses of CP and AgNPs (six days of exposure, Group 5). Blood samples were taken just before the first administration (0 h) and every 24 h for seven days. Our results show that Argovit™ AgNPs induced no significant cytotoxic or acute genotoxic damage. The observed cumulative genotoxic damage in this model could be caused by the accumulation of AgNPs due to administered consecutive doses. Furthermore, the administration of AgNPs after 24 h of CP seems to have a protective effect on bone marrow and reduces by up to 50% the acute genotoxic damage induced by CP. However, this protection is not enough to counteract several doses of CP. To our knowledge, this is the first time that the exceptional chemoprotective capacity produced by a non-cytotoxic silver nanoparticle formulation against CP genotoxic damage has been reported. These findings raise the possibility of using AgNPs as an adjuvant agent with current treatments, reducing adverse effects.

New Protein-Coated Silver Nanoparticles: Characterization, Antitumor and Amoebicidal Activity, Antiproliferative Selectivity, Genotoxicity, and Biocompatibility Evaluation.

Nanomaterials quickly evolve to produce safe and effective biomedical alternatives, mainly silver nanoparticles (AgNPs). The AgNPs' antibacterial, antiviral, and antitumor properties convert them into a recurrent scaffold to produce new treatment options. This work reported the full characterization of a highly biocompatible protein-coated AgNPs formulation and their selective antitumor and amoebicidal activity. The protein-coated AgNPs formulation exhibits a half-inhibitory concentration (IC50) = 19.7 µM (2.3 µg/mL) that is almost 10 times more potent than carboplatin (first-line chemotherapeutic agent) to inhibit the proliferation of the highly aggressive human adenocarcinoma HCT-15. The main death pathway elicited by AgNPs on HCT-15 is apoptosis, which is probably stimulated by reactive oxygen species (ROS) overproduction on mitochondria. A concentration of 111 µM (600 µg/mL) of metallic silver contained in AgNPs produces neither cytotoxic nor genotoxic damage on human peripheral blood lymphocytes. Thus, the AgNPs formulation evaluated in this work improves both the antiproliferative potency on HCT-15 cultures and cytotoxic selectivity ten times more than carboplatin. A similar mechanism is suggested for the antiproliferative activity observed on HM1-IMSS trophozoites (IC50 = 69.2 µM; 7.4 µg/mL). There is no change in cell viability on mice primary cultures of brain, liver, spleen, and kidney exposed to an AgNPs concentration range from 5.5 µM to 5.5 mM (0.6 to 600 µg/mL). The lethal dose was determined following the OECD guideline 420 for Acute Oral Toxicity Assay, obtaining an LD50 = 2618 mg of Ag/Kg body weight. All mice survived the observational period; the histopathology and biochemical analysis show no differences compared with the negative control group. In summary, all results from toxicological evaluation suggest a Category 5 (practically nontoxic) of the Globally Harmonized System of Classification and Labelling of Chemicals for that protein-coated AgNPs after oral administration for a short period and urge the completion of its preclinical toxicological profile. These findings open new opportunities in the development of selective, safe, and effective AgNPs formulations for the treatment of cancer and parasitic diseases with a significant reduction of side effects.

Green synthesis of silver nanoparticles using Lysiloma acapulcensis exhibit high-antimicrobial activity.

The scientific community is exploiting the use of silver nanoparticles (AgNPs) in nanomedicine and other AgNPs combination like with biomaterials to reduce microbial contamination. In the field of nanomedicine and biomaterials, AgNPs are used as an antimicrobial agent. One of the most effective approaches for the production of AgNPs is green synthesis. Lysiloma acapulcensis (L. acapulcensis) is a perennial tree used in traditional medicine in Mexico. This tree contains abundant antimicrobial compounds. In the context of antimicrobial activity, the use of L. acapulcensis extracts can reduce silver to AgNPs and enhance its antimicrobial activity. In this work, we demonstrate such antimicrobial activity effect employing green synthesized AgNPs with L. acapulcensis. The FTIR and LC-MS results showed the presence of chemical groups that could act as either (i) reducing agents stabilizing the AgNPs or (ii) antimicrobial capping agents enhancing antimicrobial properties of AgNPs. The synthesized AgNPs with L. acapulcensis were crystalline with a spherical and quasi-spherical shape with diameters from 1.2 to 62 nm with an average size diameter of 5 nm. The disk diffusion method shows the magnitude of the susceptibility over four pathogenic microorganisms of clinical interest. The antimicrobial potency obtained was as follows: E. coli ≥ S. aureus ≥ P. aeruginosa > C. albicans. The results showed that green synthesized (biogenic) AgNPs possess higher antimicrobial potency than chemically produced AgNPs. The obtained results confirm a more significant antimicrobial effect of the biogenic AgNPs maintaining low-cytotoxicity than the AgNPs produced chemically.

Argovit™ Silver Nanoparticles Effects on Allium cepa: Plant Growth Promotion without Cyto Genotoxic Damage.

Due to their antibacterial and antiviral effects, silver nanoparticles (AgNP) are one of the most widely used nanomaterials worldwide in various industries, e.g., in textiles, cosmetics and biomedical-related products. Unfortunately, the lack of complete physicochemical characterization and the variety of models used to evaluate its cytotoxic/genotoxic effect make comparison and decision-making regarding their safe use difficult. In this work, we present a systematic study of the cytotoxic and genotoxic activity of the commercially available AgNPs formulation Argovit™ in Allium cepa. The evaluated concentration range, 5-100 µg/mL of metallic silver content (85-1666 µg/mL of complete formulation), is 10-17 times higher than the used for other previously reported polyvinylpyrrolidone (PVP)-AgNP formulations and showed no cytotoxic or genotoxic damage in Allium cepa. Conversely, low concentrations (5 and 10 µg/mL) promote growth without damage to roots or bulbs. Until this work, all the formulations of PVP-AgNP evaluated in Allium cepa regardless of their size, concentration, or the exposure time had shown phytotoxicity. The biological response observed in Allium cepa exposed to Argovit™ is caused by nanoparticles and not by silver ions. The metal/coating agent ratio plays a fundamental role in this response and must be considered within the key physicochemical parameters for the design and manufacture of safer nanomaterials.

Cytokinesis-Block Micronucleus Assay Using Human Lymphocytes as a Sensitive Tool for Cytotoxicity/Genotoxicity Evaluation of AgNPs.

Silver nanoparticles (AgNPs) are the most used nanomaterials worldwide due to their excellent antibacterial, antiviral, and antitumor activities, among others. However, there is scarce information regarding their genotoxic potential measured using human peripheral blood lymphocytes. In this work, we present the cytotoxic and genotoxic behavior of two commercially available poly(vinylpyrrolidone)-coated silver nanoparticle (PVP-AgNPs) formulations that can be identified as noncytotoxic and nongenotoxic by just evaluating micronuclei (MNi) induction and the mitotic index, but present enormous differences when other parameters such as cytostasis, apoptosis, necrosis, and nuclear damage (nuclear buds (NBUDs) and nucleoplasmic bridges (NPBs)) are analyzed. The results show that Argovit (35 nm PVP-AgNPs) and nanoComposix (50 nm PVP-AgNPs), at concentrations from 0.012 to 12 µg/mL, produce no changes in the nuclear division index (NDI) or micronuclei (MNi) frequency compared with the values found on control cultures of human blood peripheral lymphocytes from a healthy donor. Still, 50 nm PVP-AgNPs significantly decrease the replication index and significantly increase cytostasis, apoptosis, necrosis, and the frequencies of nuclear buds (NBUDs) and nucleoplasmic bridges (NPBs). These results provide evidence that the cytokinesis-block micronucleus (CBMN) assay using human lymphocytes and evaluating the eight parameters provided by the technique is a sensitive, fast, accurate, and inexpensive detection tool to support or discard AgNPs or other nanomaterials, which is worthwhile for continued testing of their effectiveness and toxicity for biomedical applications. In addition, it provides very important information about the role played by the [coating agent]/[metal] ratio in the design of nanomaterials that could reduce adverse effects as much as possible while retaining their therapeutic capabilities.

Electrospun Fibers and Sorbents as a Possible Basis for Effective Composite Wound Dressings.

Skin burns and ulcers are considered hard-to-heal wounds due to their high infection risk. For this reason, designing new options for wound dressings is a growing need. The objective of this work is to investigate the properties of poly (ε-caprolactone)/poly (vinyl-pyrrolidone) (PCL/PVP) microfibers produced via electrospinning along with sorbents loaded with Argovit™ silver nanoparticles (Ag-Si/Al2O3) as constituent components for composite wound dressings. The physicochemical properties of the fibers and sorbents were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and inductively coupled plasma optical emission spectroscopy (ICP-OES). The mechanical properties of the fibers were also evaluated. The results of this work showed that the tested fibrous scaffolds have melting temperatures suitable for wound dressings design (58-60 °C). In addition, they demonstrated to be stable even after seven days in physiological solution, showing no macroscopic damage due to PVP release at the microscopic scale. Pelletized sorbents with the higher particle size demonstrated to have the best water uptake capabilities. Both, fibers and sorbents showed antimicrobial activity against Gram-negative bacteria Pseudomona aeruginosa and Escherichia coli, Gram-positive Staphylococcus aureus and the fungus Candida albicans. The best physicochemical properties were obtained with a scaffold produced with a PCL/PVP ratio of 85:15, this polymeric scaffold demonstrated the most antimicrobial activity without affecting the cell viability of human fibroblast. Pelletized Ag/Si-Al2O3-3 sorbent possessed the best water uptake capability and the higher antimicrobial activity, over time between all the sorbents tested. The combination of PCL/PVP 85:15 microfibers with the chosen Ag/Si-Al2O3-3 sorbent will be used in the following work for creation of wound dressings possessing exudate retention, biocompatibility and antimicrobial activity.

Heteroleptic NiII complexes: Synthesis, structural characterization, computational studies and amoebicidal activity evaluation.

In this work, we present the synthesis, characterization, electrochemical studies, DFT calculations, and in vitro amoebicidal effect of seven new heteroleptic NiII coordination compounds. The crystal structures of [H2(pdto)](NO3)2 and [Ni(pdto)(NO3)]PF6 are presented, pdto = 2,2'-[1,2-ethanediylbis-(sulfanediyl-2,1-ethanediyl)]dipyridine. The rest of the compounds have general formulae: [Ni(pdto)(NN)](PF6) where N-N = 2,2'-bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (44dmbpy), 5,5'-dimethyl-2,2'-bipyridine (55dmbpy), 1,10-phenanthroline (phen), 4,7-dimethyl-1,10-phenanthroline (47dmphen) and 5,6-dimethyl-1,10-phenanthroline (56dmphen). The size of NN ligand and its substituents modulate the compound electronic features and influence their antiproliferative efficiency against Entamoeba histolytica. 56dmphen derivative, shows the biggest molar volume and presents a powerful amoebicidal activity (IC50 = 1.2 µM), being seven times more effective than the first-line drug for human amoebiasis metronidazole. Also, increases the reactive oxygen species concentration within the trophozoites. This could be the trigger of the E. histolytica growth inhibition. The antiparasitic effect is described using NiII electron density, molar volume, estimated by DFT, as well as the experimental redox potential and diffusion coefficients. In general, amoebicidal efficiency is directly proportional to the increment of the molar volume and decreases when the redox potential becomes more positive.

Argovit™ silver nanoparticles to fight Huanglongbing disease in Mexican limes (Citrus aurantifolia Swingle).

Nowadays, Huanglongbing (HLB) disease, commonly known as "yellow dragon disease", affects citrus crops worldwide and has a devastating effect in the agro-industrial sector. Significant efforts have been made to fight the illness, but still, there is no effective treatment to eradicate the disease. This work is the first approach to evaluate the capacity of silver nanoparticles (AgNPs) to directly eradicate the bacteria responsible for Huanglongbing disease, Candidatus Liberibacter asiaticus (CLas), in the field. The AgNPs were administered by foliar sprinkling and trunk injection of 93 sick trees with remarkable results. Both methods produce an 80-90% decrease of bacterial titre, quantified by qRT-PCR in collected foliar tissue, compared with the control group. Scanning electron microscopy images show an essential reduction of starch accumulation in phloem vessels after AgNP treatments without evidence of bacteria in the analyzed samples. Compared with other effective methods that involve ß-lactam antibiotics, the potency of AgNPs is 3 to 60-times higher when it is administered by foliar sprinkling and from 75 to 750-fold higher when the administration was by trunk-injection. All these results allow us to propose this AgNP formulation as a promising alternative for the treatment of infected trees in the field.

Antiproliferative and Antitumour Effect of Nongenotoxic Silver Nanoparticles on Melanoma Models.

During the last 3 decades, there has been a slow advance to obtain new treatments for malignant melanoma that improve patient survival. In this work, we present a systematic study focused on the antiproliferative and antitumour effect of AgNPs. These nanoparticles are fully characterized, are coated with polyvinylpyrrolidone (PVP), and have an average size of 35 ± 15 nm and a metallic silver content of 1.2% wt. Main changes on cell viability, induction of apoptosis and necrosis, and ROS generation were found on B16-F10 cells after six hours of exposure to AgNPs (IC50 = 4.2 µg/mL) or Cisplatin (IC50 = 2.0 µg/mL). Despite the similar response for both AgNPs and Cisplatin on antiproliferative potency (cellular viability of 53.95 ± 1.88 and 53.62 ± 1.04) and ROS production (20.27 ± 1.09% and 19.50 ± 0.35%), significantly different cell death pathways were triggered. While AgNPs induce only apoptosis (45.98 ± 1.88%), Cisplatin induces apoptosis and necrosis at the same rate (22.31 ± 1.72% and 24.07 ± 1.10%, respectively). In addition to their antiproliferative activity, in vivo experiments showed that treatments of 3, 6, and 12 mg/kg of AgNPs elicit a survival rate almost 4 times higher (P < 0.05) compared with the survival rate obtained with Cisplatin (2 mg/kg). Furthermore, the survivor mice treated with AgNPs do not show genotoxic damage determined by micronuclei frequency quantification on peripheral blood cells. These results exhibit the remarkable antitumour activity of a nongenotoxic AgNP formulation and constitute the first advance toward the application of these AgNPs for melanoma treatment, which could considerably reduce adverse effects provoked by currently applied chemotherapeutics.

Antigiardiasic activity of Cu(II) coordination compounds: Redox imbalance and membrane damage after a short exposure time.

Giardiasis is a widespread illness that affects inhabitants of underdeveloped countries, being children and seniors the highest risk population. The several adverse effects produced by current therapies besides its increasing ineffectiveness due to the appearance of resistant strains evidence the urgent need for new therapeutic approaches. We present the antigiardiasic effect of eight Cu(II) coordination compounds, which belong to the family Casiopeínas. Two of them, 4,7-diphenyl-1,10-phenanthroline(acetylacetonato)copper(II) nitrate (CasIII-Ha,36 µM) and 4,7-diphenyl-1,10-phenanthroline(glycinato)copper(II) nitrate (CasI-gly,36 µM) have shown the best antiproliferative effect in Giardia intestinalis trophozoite cultures, both with the higher lipophilic character of the series. The antiproliferative effect of these coordination compounds is attributable to its capacity to interact with the cellular membrane and to increase reactive oxygen species (ROS) concentration within the parasite since the first hours of exposure, (2-6 h). We found that these compounds mainly induced the cell death of trophozoites by apoptosis, contrary to metronidazole, which induces apoptosis and necrosis in the same ratio. The cytotoxic effects on lymphocytes and macrophages isolated from human peripheral blood allowed us to establish a selectivity index and in turn, identify and propose the best candidates to continue with the assays in animal models. The selected molecules do not include the most active compounds against trophozoites, instead of that, we propose the compounds 4',4'-dimethyl-2,2'-bipyridine(acetylacetonato)copper(II) nitrate (CasIII-ia,IC50 = 156 µM) and 4,7-dimethyl-1,10-phenanthroline(acetylacetonato) copper(II) nitrate (CasIII-Ea,IC50 = 125 µM), which possess an antiproliferative efficacy comparable with Metronidazole but also are those that produce the lowest effect on the viability of human lymphocytes and macrophages.

Toxicity of silver nanoparticles in mouse bone marrow-derived dendritic cells: Implications for phenotype.

Silver nanoparticles (AgNP) are one of the most studied nanoparticles due to their anti-bacterial, -fungal, -viral, -parasitic, and -inflammatory properties. This raises the need to evaluate the toxicity and biological effects of AgNP in the immune system in order to develop new safer biomedical products. In this study, an AgNP formulation currently approved for veterinary applications was applied to mouse bone marrow-derived dendritic cells (BMDC), considered important antigen-presenting cells of the immune system, to evaluate cytotoxicity, genotoxicity, and any significant influence on expression of cellular markers associated with BMDC phenotype and maturation status. The results showed that after 12 h of AgNP exposure, a significant decrease in BMDC viability occurred at the highest concentration tested (1.0 µg AgNP/ml) and at lower doses, the cells maintained membrane integrity and metabolic activity. DNA damage was not significant with any AgNP level aside from the 1.0 µg AgNP/ml level. Regarding phenotype, no differences in expression of CD40 (co-stimulatory molecule highly present in mature BMDC) or in CD273 (a marker for inhibitory T-cell response) were observed. The current results showed that the toxicity of this AgNP formulation was dose-related. The findings also suggest BMDC could maintain structural conservation of co-stimulatory/co-inhibitory surface molecules after 12 h of exposure to this AgNP. This work represents the first step in identifying the toxic effects of this AgNP formulation on dendritic cells.