Novel Directed Enzyme Prodrug Therapy for Cancer Treatment Based on 2'-Deoxyribosyltransferase-Conjugated Magnetic Nanoparticles.

Directed enzyme prodrug therapy (DEPT) strategies show promise in mitigating chemotherapy side effects during cancer treatment. Among these, the use of immobilized enzymes on solid matrices as prodrug activating agents (IDEPT) presents a compelling delivery strategy, offering enhanced tumor targeting and reduced toxicity. Herein, we report a novel IDEPT strategy by employing a His-tagged type I 2'-deoxyribosyltransferase (His-PDT) covalently attached to glutaraldehyde-activated magnetic iron oxide nanoparticles (MIONPs).

In vitro approach to refine bioconcentration and biotransformation predictions of organic persistent pollutants using cell lines.

The application of the 3Rs (Replacement, Reduction, and Refinement) in animal experimentation has recently concentrated its efforts on utilizing cellular systems to predict toxicity in organisms. In this context, while refining the data obtained from cell lines, this study assesses their bioaccumulation potential and various methods for extrapolating the in vitro metabolization rate constant to support modelled bioaccumulation assessments for fish and their limitations. For this purpose, the concentrations of the parent compound, phenanthrene, and its major metabolites within the cells and in the medium at various exposure times were quantified.

Miniaturized method for the quantification of persistent organic pollutants and their metabolites in HepG2 cells: assessment of their biotransformation.

Biotransformation can greatly influence the accumulation and, subsequently, toxicity of substances in living beings. Although traditionally these studies to quantify metabolization of a compound have been carried out with in vivo species, currently, in vitro test methods with very different cell lines are being developed for their evaluation. However, this is still a very limited field due to multiple variables of a very diverse nature.

Bioaccumulation and Biotransformation of BDE-47 Using Zebrafish Eleutheroembryos (Danio rerio).

Polybrominated diphenyl ethers (PBDEs) are well-known endocrine disrupting chemicals identified as organic persistent pollutants. Their metabolites OH-BDE and MeO-BDE have been reported to be potentially more toxic than the postulated precursor PBDEs. One of the most predominant congeners of PBDEs in the environment is BDE-47, due to its high presence in industrially used mixtures.

Development of a method for assessing the accumulation and metabolization of antidepressant drugs in zebrafish (Danio rerio) eleutheroembryos.

Antidepressant drugs are widely used for the treatment of common mental or other psychiatric disorders such as depression, which affect about 121 million people worldwide. This widespread use has contributed to the input of these pharmaceuticals and their metabolites into the environment. The aim of this work was to develop an analytical method to quantify the most widely used antidepressant drugs, selective serotonin reuptake inhibitors (SSRI), and their main metabolites in the environment.

In vivo quantification of volatile organoselenium compounds released by bacteria exposed to selenium with HS-SPME-GC-MS. Effect of selenite and selenium nanoparticles.

Quantification of volatile organoselenium species released by Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), after their growth in the presence of 1 and 2 mg Se·L as both selenite and chitosan-modified selenium nanoparticles (Ch-SeNPs), was achieved by the application of a method based on headspace solid-phase microextraction (HS-SPME) and in-fiber internal standardization, combined with gas chromatography coupled to mass spectrometry (GC-MS).

Insights into the accumulation and transformation of Ch-SeNPs by Raphanus sativus and Brassica juncea: Effect on essential elements uptake.

Selenium (Se) at very low doses has important functions for humans. Unfortunately, the low levels of Se in soils in various regions of the world have implemented the agronomic biofortification of crops by applying Se-enriched fertilizers (mainly based on selenate). Lately, the use of nanofertilizers is growing in interest as their low size reduces the amount of chemicals and minimizes nutrient losses in comparison with conventional bulk fertilizers.

In-vivo solid phase microextraction for quantitative analysis of volatile organoselenium compounds in plants.

A new calibration method based on the use of headspace solid-phase microextraction (HS-SPME) and in-fiber internal standardization, combined with gas chromatography coupled to mass spectrometry (GC/MS) was developed for quantifying Se volatile organic species released by plants exposed to chitosan-modified selenium nanoparticles (Cs-SeNPs). The effect of several parameters affecting extraction and separation of the selected organic species of selenium (dimethylselenium (DMSe), diethylselenium (DESe) and dimethyldiselenium (DMDSe)) and deuterated dimethyl sulphide (d-DMS) employed as internal standard were studied and optimized using an experimental design. The developed methodology was applied for quantifying the volatile selenium compounds produced over time by the plant species Raphanus sativus and Brassica juncea grown in hydroponic solution containing 5 mg Se L in the form Cs-SeNPs.

Impact of selenium co-administration on methylmercury exposed eleutheroembryos and adult zebrafish (Danio rerio): Changes in bioaccumulation and gene expression.

Mercury still represents one of the most hazardous threats for the aquatic ecosystem due to its high toxicity, and the fact that it can be easily incorporated into the food chain by accumulation in fish as MeHg. On the other hand, selenium is a micronutrient that is part of different antioxidant enzymes that regulate the cellular redox state, and whose complex interaction with Hg has been extensively studied from a toxicological point of view. In order to evaluate the protective effect of Se(IV) co-administration against MeHg accumulation and toxicity, we have selected an in-vivo model at two developmental stages: zebrafish eleutheroembryos and adult fish.

In vivo bioconcentration of a metal mixture by Danio rerio eleutheroembryos.

Exposure to heavy metals has represented one of the most serious health risks of environmental pollution over the last 50 years. Most of the bioconcentration studies that have been carried out to date explored only individual contaminants, unlike the real situations that occur in the environment. In this work, zebrafish eleutheroembryos were exposed to a mixture of CHHg(II), iAs(III), Ag(I) and Cd(II), and new BCFs were calculated and compared with those calculated from single metal exposures.

Detection of exposure effects of mixtures of heavy polycyclic aromatic hydrocarbons in zebrafish embryos.

In this study we evaluated the exposure effects of mixtures of five polycyclic aromatic hydrocarbons (PAHs); namely, benzo[a]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[k]fluoranthene and chrysene on zebrafish embryos. Supplementation of the exposure media with 0.45% dimethyl sulfoxide and 50 ppm of Tween 20 could guarantee the solubilization and stabilization of the PAHs up to 24 h without affecting the embryos development.

Method for quantifying NSAIDs and clofibric acid in aqueous samples, lumpfish (Cyclopterus lumpus) roe, and zebrafish (Danio rerio) eleutheroembryos and evaluation of their bioconcentration in zebrafish eleutheroembryos.

Pharmaceuticals such as nonsteroidal anti-inflammatory drugs (NSAIDs) and lipid regulators are being repeatedly detected at low concentrations (pg · mL-ng · mL) in the environment. A large fraction of these compounds are ionizable. Ionized compounds show different physico-chemical properties and environmental behavior in comparison to their neutral analogs; as a consequence, the quantification methods currently available, based on the neutral molecules, might not be suitable to detect the corresponding ionized compounds.

Bioconcentration of ionic cadmium and cadmium selenide quantum dots in zebrafish larvae.

The concern related to the use of nanomaterials is growing nowadays, especially the risk associated with their emission or exposure. One type of nanomaterials that has attracted much attention is quantum dots (QDs). QDs incorporation in consumer goods increases the probability of their entering in the environment and then into living organisms and human.

Evaluation of chromatographic columns packed with semi- and fully porous particles for benzimidazoles separation.

The behavior of 15 benzimidazoles, including their main metabolites, using several C18 columns with standard or narrow-bore diameters and different particle size and type were evaluated. These commercial columns were selected because their differences could affect separation of benzimidazoles, and so they can be used as alternative columns. A simple screening method for the analysis of benzimidazole residues and their main metabolites was developed.

Zebrafish (Danio rerio) eleutheroembryo-based procedure for assessing bioaccumulation.

This paper reports on the development and preliminary evaluation of a new bioaccumulation test based on the use of zebrafish (Danio renio) eleutheroembryos (72 h after hatching, corresponding to 144 h post fertilization, hpf) as an alternative to adult fish-based procedures for regulatory purposes regarding REACH application. The proposed test accomplished the OECD 305 guideline and consists of a 48 h uptake period followed by a 24 h depuration step. Bioaccumulation experiments were performed for a selected of hyper hydrophobic chemicals (log Kow> 7.

Bioaccumulation of ionic titanium and titanium dioxide nanoparticles in zebrafish eleutheroembryos.

The production of titanium dioxide nanoparticles (TiO(2) NPs) for commercial applications has greatly increased over the last years and consequently the potential risk for human health. There is a growing awareness of the need to understand the behavior and influence these nanoparticles exert on the environment. Bioaccumulation serves as a good integrator to assess chemical exposure in aquatic systems and is dependent on factors, such as the exposure routes, diet and the aqueous medium.

Comparison of bioconcentration of ionic silver and silver nanoparticles in zebrafish eleutheroembryos.

The production of silver nanoparticles has reached nowadays high levels. Bioconcentration studies, information on persistence and toxicity are fundamental to assess their global risk and thus necessary to establish legislations regarding their use. Previous studies on silver nanoparticle toxicity have determined a clear correlation between their chemical stability and toxicity.

Analytical performance of two miniaturised extraction methods for triclosan and methyltriclosan, in fish roe and surimi samples.

A new and reliable miniaturised QuEChERS-based extraction method combined with a dispersive SPE cleanup procedure for extracting triclosan and methyltriclosan from fish roe and surimi samples was proposed. The effectiveness of different extraction/partition conditions for QuEChERS method was systematically investigated, and the use of acetonitrile extraction solvent and MgSO4, PSA, C18 and Florisil as cleanup reagents was recommended in the final method. Other method based on ultrasonic extraction with ethylacetate and clean-up with SPE was also evaluated for these samples.

Rapid determination of polycyclic aromatic hydrocarbons (PAHs) in zebrafish eleutheroembryos as a model for the evaluation of PAH bioconcentration.

A simple and fast approach for a novel bioaccumulation test by exposing zebrafish eleutheroembryos to fluorene and anthracene (PAHs) at two concentration levels below 1% of their LC50 is presented. This alternative protocol sets an uptake period of 48 h at 26 °C for bioconcentration of the compounds tested and an additional 24h for depuration. Two different methods to estimate bioconcentration factors (BCFs) of PAHs were used.

Bioconcentration of pesticides in zebrafish eleutheroembryos (Danio rerio).

The feasibility of a bioaccumulation test based on the use of zebrafish eleutheroembryos as an alternative to adult-individual-based approaches for REACH application has been evaluated for three test compounds, chlorpyrifos, dicofol and atrazine. Following the OECD 305 guidelines, zebrafish eleutheroembryos (72 h after hatching, hpf) were separately exposed to the investigated pesticides at two nominal concentrations below 1% of its corresponding LC(50). The uptake experiments lasted for 48 h.

Miniaturized extraction methods of triclosan from aqueous and fish roe samples. Bioconcentration studies in zebrafish larvae (Danio rerio).

Triclosan, an antibacterial and antifungal agent, is widely used in household and personal care products, processed foods and food packaging, etc., and thus also released into the environment. Triclosan is acutely and chronically toxic to aquatic organisms and bioaccumulates in fish tissue.

Bioaccumulation and transformation of methylmercury and selenite using zebrafish (Danio Rerio) larvae as a model.

Bioaccumulation and possible transformation of methylmercury and selenite has been checked on a 72 h-cycle of bioaccumulation and depuration using larvae from zebrafish. The larvae were exposed to methylmercury and selenite at concentrations of 1% and 0.1% of their LC(50) values.

Zebrafish larvae as a model for the evaluation of inorganic arsenic and tributyltin bioconcentration.

The European REACH legislation establishes the need to study the toxicity, persistence and bioaccumulation of those chemicals with an exceeding production of 100tons and/or chemicals considered PBTs substances (Persistence, Bioaccumulation and Toxicity). Currently, the OECD technical guideline 305 is the most used protocol to determine bioconcentration factors of contaminants in aquatic environments. However, this procedure implies high cost and amount of adult fishes.

Miniaturisated method for the analysis of polycyclic aromatic hydrocarbons in leaf samples.

A new methodology is proposed for monitoring 16 priority polycyclic aromatic hydrocarbons, using tree leaves as passive samplers, by means of a mini-ultrasonic probe coupled with reversed-phase liquid chromatography (RP-LC) and fluorescence (FL) detection. Separation and detection of the 16 PAHs were completed in 19 min, using a 3 microm (particle size) C(18) column RP-LC with acetonitrile-water gradient elution. The ultrasonic probe device used was equipped with a 2 mm titanium tip, and sample and solvent amounts used were just 50 mg and 1 mL, respectively.