Search Results (62)

This study evaluated the bioavailability, antioxidant response, and post-withdrawal retention of red and grey selenium nanoparticles (SeNPs) in adult male Japanese quails. Birds were fed a basal diet supplemented with 0.5 or 5 mg/kg of red or grey SeNPs for 28 days, followed by a 7-day withdrawal period. Selenium distribution varies markedly by nanoparticle form and dose. Red SeNPs, particularly at 5 mg/kg, produced higher selenium accumulation in metabolic and circulating tissues, whereas grey SeNPs showed lower initial uptake but more selective deposition at specific sites. Antioxidant analysis revealed significant increases in hepatic GPx activity across all SeNP groups, with the strongest enhancement occurring at the 5 mg/kg level. Serum TAC was elevated predominantly in quails receiving high-dose red SeNPs. Retention–depletion analysis demonstrated that moderate doses supported stable selenium incorporation, whereas high doses resulted in accelerated post-withdrawal loss. Overall, red SeNPs acted as rapidly available selenium sources with pronounced antioxidant effects, while grey SeNPs provided slower, more sustained selenium delivery. These findings highlight the importance of nanoparticle form and dosage in optimizing selenium supplementation strategies for poultry. Full article

Silver nanoparticles (Ag-NPs) are emerging as natural antimicrobial growth promoters in poultry, known for enhancing gut health, immunity, and productivity. This study assessed the effects of Ag-NPs and silver nitrate (AgNO₃) on sexual behavior, productivity, and silver bioaccumulation in the reproductive tissues of Japanese quails (Coturnix japonica). A total of 600 quails (8 weeks old) were randomly assigned to five groups (120 birds/group), each with six replicates (sex ratio 5 male: 15 females). Group 1 (control) received a basal diet, while Groups 2 and 3 were supplemented with Ag-NPs at 10 mg/kg and 20 mg/kg, respectively. Groups 4 and 5 received AgNO₃ at the same doses for eight weeks. Quails receiving 10 mg/kg Ag-NPs showed significantly improved male mating behavior, increased egg weight and mass, and enhanced egg quality, resulting in the highest fertility and hatchability performance. Silver accumulation in ovaries and testes increased dose-dependently, with the highest deposition observed in the 20 mg/kg Ag-NPs group. Correlation and regression analyses revealed weak and statistically non-significant relationships between ovarian silver levels and fertility and hatchability outcomes. These findings suggested that supplementation with 10 mg/kg Ag-NPs was a safe and effective feed additive for improving both productive and reproductive performance in Japanese quails. Full article

Superparamagnetic iron oxide (SPIO) nanoparticles are a promising platform for drug delivery and magnetic resonance imaging (MRI). However, complement activation and immune recognition remain major barriers to their clinical translation. Previously, we reported that dextran-coated SPIO nanoworms (NWs) trigger potent complement activation and infusion reactions. Here, we systematically map the temporal sequence of immune events following SPIO NW administration, including C3 opsonization, granulocyte uptake, and cytokine release. In both in vitro and in vivo models, C3 deposition occurred rapidly, peaking at approximately 5 min post-incubation or post-injection. Higher Fe/plasma ratios led to reduced C3 deposition per particle, although the absolute amount of C3 bound was greater in vivo than in vitro. Notably, C3 dissociation from the particle surface exhibited a consistent half-life of ~14 min, independent of the NW injected dose and circulation time. Immune uptake by blood granulocytes was delayed relative to opsonization, becoming prominent only at 60 min post-injection. Further, cytokine release, measured by plasma IL-6 levels, displayed an even slower profile, with peak expression at 6 h post-injection. Together, these results reveal a distinct sequential immune response to SPIO NWs: rapid C3 opsonization, delayed cellular uptake, and late cytokine response. Understanding these dynamics provides a basis for developing strategies to inhibit complement activation and improve the hemocompatibility of SPIO-based theranostic agents. Full article

Objective: This review provides an overview of the current knowledge regarding the mechanisms of action of AGuIX, a clinical-stage theranostic nano-radiosensitizer composed of gadolinium. It covers the steps following the administration, from the internalization in tumor cells to the interaction with X-rays and the subsequent physical, chemical, biological, and immunological events. Results: After intravenous injection, AGuIX accumulates in tumors through the enhanced permeability and retention (EPR) effect, and its specific retention properties allow its persistence in tumors for several days. At the cellular level, the nanomedicine is internalized by endocytic processes and mainly located in the cytoplasm, especially in lysosomes. AGuIX enhances the effects of radiotherapy (RT) at several levels, starting from radiation–matter interactions to a chemical stage of reactive oxygen species (ROS) production, followed by a cascade of biological events leading to tumor cell death and immune response. Indeed, AGuIX induces a local increase in radiation dose deposition through the emission of Auger electrons, leading to a subsequent increase in ROS generation. AGuIX also impacts RT-induced biological mechanisms, including DNA damage and cell death mechanisms such as apoptosis, autophagic cell death, and ferroptosis. Last, the combination of AGuIX and RT stimulates an antitumor immune response through the induction of immunogenic cell death (ICD), the activation of dendritic and T cells, and the reprogramming of tumor-associated macrophages (TAMs) into a pro-inflammatory phenotype. Conclusions: AGuIX is a clinical-stage nanoparticle (NP) intravenously administered with pan-cancer potential due to its specific biodistribution properties and a strong ability to amplify RT-induced mechanisms. Full article

Apart from HER2-positive, triple-negative breast cancer (TNBC) is the second most highly invasive type of breast cancer. Although TNBC does not overexpress HER2 receptors, it has been observed that EGFR protein expression is present in this specific type of tumor, making it an attractive target for immune and radiopharmaceutical treatments. In our current study, we used ¹⁰⁹Pd (T_1/2 = 13.7 h) in the form of a ¹⁰⁹Pd/^109mAg in vivo generator as a source of β⁻ particles and Auger electrons in targeted radionuclide therapy for TNBC. ¹⁰⁹Pd, obtained through neutron irradiation of the ¹⁰⁸Pd target, was deposited onto 15 nm gold nanoparticles to form Au@¹⁰⁹Pd core–shell nanoparticles, which were then conjugated to the panitumumab antibody. Au@¹⁰⁹Pd-PEG-panitumumab nanoparticles were bound, internalized, and partially routed to the nucleus in MDA-MB-231 human breast cancer cells overexpressing EGFR receptors. The Au@¹⁰⁹Pd-panitumumab radioconjugate significantly reduced the metabolic activity of MDA-MB-231 cells in a dose-dependent manner. In conclusion, we have found that Au@¹⁰⁹Pd-PEG-panitumumab nanoparticles show potential as a therapeutic agent for combined β⁻–Auger electron targeted radionuclide therapy of TNBC. The simultaneous emission of β⁻, conversion, and Auger electrons from the ¹⁰⁹Pd/^109mAg generator, similar to ¹⁶¹Tb conjugates, significantly enhances the therapeutic effect. The partial localization of these nanoparticles into the cell nucleus, provided by the panitumumab vector, ensures effective therapy with Auger electrons. This is particularly important for the treatment of drug-resistant TNBC cells. Full article

Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a ^99mTc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration. Full article

Methodologies across the dispersion preparation, characterization, and cellular dosimetry of hydrophilic nanoparticles (NPs) have been developed and used extensively in the field of nanotoxicology. However, hydrophobic NPs pose a challenge for dispersion in aqueous culture media using conventional methods that include sonication followed by mixing in the culture medium of interest and cellular dosimetry. In this study, a robust methodology for the preparation of stable dispersions of hydrophobic NPs for cellular studies is developed by introducing continuous energy over time via stirring in the culture medium followed by dispersion characterization and cellular dosimetry. The stirring energy and the presence of proteins in the culture medium result in the formation of a protein corona around the NPs, stabilizing their dispersion, which can be used for in vitro cellular studies. The identification of the optimal stirring time is crucial for achieving dispersion and stability. This is assessed through a comprehensive stability testing protocol employing dynamic light scattering to evaluate the particle size distribution stability and polydispersity. Additionally, the effective density of the NPs is obtained for the stable NP dispersions using the volumetric centrifugation method, while cellular dosimetry calculations are done using available cellular computational modeling, mirroring approaches used for hydrophilic NPs. The robustness of the proposed dispersion approach is showcased using a highly hydrophobic NP model (black carbon NPs) and two culture media, RPMI medium and SABM, that are widely used in cellular studies. The proposed approach for the dispersion of hydrophobic NPs results in stable dispersions in both culture media used here. The NP effective density of 1.03–1.07 g/cm³ measured here for black carbon NPs is close to the culture media density, resulting in slow deposition on the cells over time. So, the present methodology for dispersion and dosimetry of hydrophobic NPs is essential for the design of dose–response studies and overcoming the challenges imposed by slow particle deposition. Full article

Carditis in childhood is a rare disease with several etiologies. We report a case of infant death due to pericarditis and myocarditis after the mRNA vaccine against COVID-19 (COVIDmRNAV). A 7-year-old male child received the first dose of the COVIDmRNAV and presented with monoarthritis and a fever non-responsive to oral antibiotics. The laboratory investigation showed signs of infection (leukocytosis, high levels of c-reactive protein). His condition rapidly deteriorated, and the patient died. The autopsy identified pericardial fibrin deposits, hemorrhagic areas in the myocardium, and normal valves. A diffuse intermyocardial inflammatory infiltrate composed of T CD8+ lymphocytes and histiocytes was identified. An antistreptolysin O (ASO) dosage showed high titers. The presence of arthritis, elevated ASO, and carditis fulfills the criteria for rheumatic fever. However, valve disease and Aschoff’s nodules, present in 90% of rheumatic carditis cases, were absent in this case. The temporal correlation with mRNA vaccination prompted its inclusion as one of the etiologies. In cases of myocardial damage related to COVID-19mRNAV, it appears to be related to the expression of exosomes and lipid nanoparticles, leading to a cytokine storm. The potential effects of the COVID-19mRNAV must be considered in the pathogenesis of this disease, whether as an etiology or a contributing factor to a previously initiated myocardial injury. Full article

Cancer is defined as the uncontrolled proliferation of heterogeneous cell cultures in the body that develop abnormalities and mutations, leading to their resistance to many forms of treatment. Left untreated, these abnormal cell growths can lead to detrimental and even fatal complications for patients. Radiation therapy is involved in around 50% of cancer treatment workflows; however, it presents significant recurrence rates and normal tissue toxicity, given the inevitable deposition of the dose to the surrounding healthy tissue. Chemotherapy is another treatment modality with excessive normal tissue toxicity that significantly affects patients’ quality of life. To improve the therapeutic efficacy of radiotherapy and chemotherapy, multiple conjunctive modalities have been proposed, which include the targeting of components of the tumour microenvironment inhibiting tumour spread and anti-therapeutic pathways, increasing the oxygen content within the tumour to revert the hypoxic nature of the malignancy, improving the local dose deposition with metal nanoparticles, and the restriction of the cell cycle within radiosensitive phases. The tumour microenvironment is largely responsible for inhibiting nanoparticle capture within the tumour itself and improving resistance to various forms of cancer therapy. In this review, we discuss the current literature surrounding the administration of molecular and nanoparticle therapeutics, their pharmacokinetics, and contrasting mechanisms of action. The review aims to demonstrate the advancements in the field of conjugated nanomaterials and radiotherapeutics targeting, inhibiting, or bypassing the tumour microenvironment to promote further research that can improve treatment outcomes and toxicity rates. Full article

Cervical cancer remains a pressing global health concern, necessitating advanced therapeutic strategies. Radiotherapy, a fundamental treatment modality, has faced challenges such as targeted dose deposition and radiation exposure to healthy tissues, limiting optimal outcomes. To address these hurdles, nanomaterials, specifically gold nanoparticles (AuNPs), have emerged as a promising avenue. This study delves into the realm of cervical cancer radiotherapy through the meticulous exploration of AuNPs’ impact. Utilizing ex vivo experiments involving cell lines, this research dissected intricate radiobiological interactions. Detailed scrutiny of cell survival curves, dose enhancement factors (DEFs), and apoptosis in both cancer and normal cervical cells revealed profound insights. The outcomes showcased the substantial enhancement of radiation responses in cancer cells following AuNP treatment, resulting in heightened cell death and apoptotic levels. Significantly, the most pronounced effects were observed 24 h post-irradiation, emphasizing the pivotal role of timing in AuNPs’ efficacy. Importantly, AuNPs exhibited targeted precision, selectively impacting cancer cells while preserving normal cells. This study illuminates the potential of AuNPs as potent radiosensitizers in cervical cancer therapy, offering a tailored and efficient approach. Through meticulous ex vivo experimentation, this research expands our comprehension of the complex dynamics between AuNPs and cells, laying the foundation for their optimized clinical utilization. Full article

High-atomic-number (Z) nanoparticles produce a cascade of low-energy secondary electrons and characteristic X-rays when ionized by X-ray irradiation. These secondary particles deposit their energy in the vicinity of the nanoparticles and, provided that the latter are selectively accumulated within tumor cells, this results in increased DNA damage and tumor cell deaths. This study reviews the utilization of high-Z nanoparticles in the treatment of soft tissue sarcomas (STS). Both in vitro and in vivo experiments demonstrated that the dose is enhanced by approximately 1.2 when polyethelyne glycol (PEG)-modified gold nanoparticles, and from 1.4 to 1.8 when hafnium oxide nanoparticles (NBTXR3, Nanobiotix SA, France) are introduced into tumor cells and activated by X-ray beams. In a phase 2/3 clinical trial investigating the therapeutic benefit of using nanoparticles in preoperative external beam radiotherapy for locally advanced STS, the proportion of patients with a pathological complete response in their resected tumor was doubled when NBTXR3 nanoparticles were used. Additionally, a higher percentage of patients with complete tumor resection was observed in the NBTXR3 plus radiotherapy group. Similar toxicity profiles were found for both the NBTXR3 plus radiotherapy and the radiotherapy alone patient groups. The incorporation of radio-sensitizing nanoparticles in the preoperative radiotherapy of STS could enhance treatment outcomes. Full article

Background: Heavy ion irradiation (IR) with high-linear energy transfer (LET) is characterized by a unique depth dose distribution and increased biological effectiveness. Following high-LET IR, localized energy deposition along the particle trajectories induces clustered DNA lesions, leading to low electron density domains (LEDDs). To investigate the spatiotemporal dynamics of DNA repair and chromatin remodeling, we established the automated image analysis of transmission electron micrographs. Methods: Human fibroblasts were irradiated with high-LET carbon ions or low-LET photons. At 0.1 h, 0.5 h, 5 h, and 24 h post-IR, nanoparticle-labeled repair factors (53BP1, pKu70, pKu80, DNA-PKcs) were visualized using transmission electron microscopy in interphase nuclei to monitor the formation and repair of DNA damage in the chromatin ultrastructure. Using AI-based software tools, advanced image analysis techniques were established to assess the DNA damage pattern following low-LET versus high-LET IR. Results: Low-LET IR induced single DNA lesions throughout the nucleus, and most DNA double-strand breaks (DSBs) were efficiently rejoined with no visible chromatin decondensation. High-LET IR induced clustered DNA damage concentrated along the particle trajectories, resulting in circumscribed LEDDs. Automated image analysis was used to determine the exact number of differently sized nanoparticles, their distance from one another, and their precise location within the micrographs (based on size, shape, and density). Chromatin densities were determined from grayscale features, and nanoparticles were automatically assigned to euchromatin or heterochromatin. High-LET IR-induced LEDDs were delineated using automated segmentation, and the spatial distribution of nanoparticles in relation to segmented LEDDs was determined. Conclusions: The results of our image analysis suggest that high-LET IR induces chromatin relaxation along particle trajectories, enabling the critical repair of successive DNA damage. Following exposure to different radiation qualities, automated image analysis of nanoparticle-labeled DNA repair proteins in the chromatin ultrastructure enables precise characterization of specific DNA damage patterns. Full article

A facile method was developed for preparing size-controlled silver nanoparticles supported by pyrolytic carbon from microcrystalline cellulose (MCC). The pyrolysis of cellulose-AgNO₃ mixture caused the oxidation of cellulose, resulting in carboxyl groups to which silver ions can bind firmly and act as nuclei for the deposition of silver nanoparticles. The structure and properties of the obtained nanocomposite were characterized by using a scanning electron microscope (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). The results suggest that silver nanoparticles were integrated successfully and dispersed uniformly in the pyrolytic carbon matrix. The average particle size varied between 20 nm and 100 nm in correlation to the dose of silver nitrate and temperature of pyrolysis. The products showed high electric conductivity and strong antimicrobial activity against Escherichia coli (E. coli). Full article

Nickel nanoparticles (NiNPs) have wide applications in industry and biomedicine due to their unique characteristics. The liver is the major organ responsible for nutrient metabolism, exogenous substance detoxification and biotransformation of medicines containing nanoparticles. Hence, it is urgent to further understand the principles and potential mechanisms of hepatic effects on NiNPs administration. In this study, we explored the liver impacts in male C57/BL6 mice through intraperitoneal injection with NiNPs at doses of 10, 20 and 40 mg/kg/day for 7 and 28 days. The results showed that NiNPs treatment increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and induced pathological changes in liver tissues. Moreover, hepatic triglyceride (TG) content and lipid droplet deposition identified via de novo lipogenesis (DNL) progression were enhanced after NiNPs injection. Additionally, sustained NiNPs exposure induced a remarkable hepatic inflammatory response, significantly promoted endoplasmic reticulum stress (ER stress) sensors Ire1α, Perk and Atf6, and activated the occurrence of liver cell apoptosis. Overall, the research indicated that NiNPs exposure induced liver injury and disturbance of lipid metabolism. These findings revealed the public hazard from extreme exposure to NiNPs and provided new information on biological toxicity and biosafety evaluation. Full article

Effective removal of toxic inorganic and organic pollutants is one of the current leading challenges of wastewater treatment. In this study, the decomposition of methylene blue (MB) under UV light irradiation was investigated in the presence of copper nanoclusters (NCs)-deposited polyethylene terephthalate (PET) track-etched hybrid membranes. PET track-etched membranes (TeMs) with an average pore size of ~400 nm were grafted by functional acrylic acid (AA) monomer under electron beam irradiation after oxidation with H₂O₂/UV system. The radiation dose varied between 46 and 200 kGy. For the deposition of copper NCs, poly(acrylic acid) (PAA)-grafted membranes saturated with Cu(II) ions were irradiated either by electron beam or γ-rays to obtain copper-based NCs for the catalytic degradation of MB. Irradiation to 100 kGy with accelerated electrons resulted in the formation of small and uniform copper hydroxide (Cu(OH)₂) nanoparticles homogeneously distributed over the entire volume of the template. On the other hand, irradiation under γ-rays yielded composites with copper NCs with a high degree of crystallinity. However, the size of the deposited NCs obtained by γ-irradiation was not uniform. Nanoparticles with the highest uniformity were obtained at 150 kGy dose. Detailed analysis by X-ray diffraction (XRD) and scanning electron microscopy (SEM) confirmed the loading of copper nanoparticles with an average size of 100 nm on the inner walls of nanochannels and on the surface of PET TeMs. Under UV light irradiation, composite membranes loaded with NCs exhibited high photocatalytic activity. It was determined that the highest catalytic activity was observed in the presence of Cu(OH)₂@PET-g-PAA membrane obtained at 250 kGy. More than 91.9% of the initial dye was degraded when this hybrid membrane was employed for 180 min, while only 83.9% of MB was degraded under UV light using Cu@PET-g-PAA membrane. Cu(OH)₂@PET-g-PAA membranes obtained under electron beam irradiation demonstrated a higher photocatalytic activity compared to Cu@PET-g-PAA membranes attained by γ-rays. Full article