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Povzetek: Graphene quantum dots (GQDs) are nanoscale carbon-based materials characterized by a tunable bandgap and unique physicochemical features. Typically composed of only a few atomic layers and measuring under 10 nm in lateral dimension, they show excellent biocompatibility and low toxicity, making them attractive for biomedical uses. Their strong photoluminescent properties support applications in optical and electrical sensing, bioimaging, cancer therapy, and the development of high‑performance nanocomposites. In this study, two types of GQDs—green‑emitting (G‑GQD) and blue‑emitting (B‑GQD)—were examined, differing primarily in their optical properties, particularly the colour of emitted light dictated by their bandgap. Potential genotoxicity was evaluated using a 3D human hepatocellular carcinoma (HepG2) spheroid model. DNA damage induction was assessed with the comet assay, after 24‑hour exposure to 12.5, 25, 50, and 100 µg/mL of B‑ and G‑GQDs. Single-cell suspensions from spheroids were obtained using a combination of mechanical disruption and enzymatic digestion (Štempar et al., 2019). Following 24-hour exposure to B- and G-GQD at concentrations of 12.5, 25, 50, and 100 µg/mL (corresponding to 5, 10, 20, and 40 µg/cm2) and 30 μg/mL BaP as the positive control, spheroids were collected and treated with a mixture of collagenase and TrypLE, diluted in serum-free medium (1:20:9), for 10 minutes. Spheroids were then mechanically dissociated into a single-cell suspension by pipetting. The subsequent steps followed the standard monolayer cell culture protocol. Briefly, 30 μL of the cell suspension was mixed with 70 μL of 1% low-melting-point (LMP) agarose and applied to fully frosted slides pre-coated with a layer of 1% normal-melting-point (NMP) agarose. The slides were lysed in a solution containing 0.1 M EDTA, 2.5 M NaOH (pH 10), 0.01 M Tris, and 1% Triton X-100 for 1 hour at 4°C. DNA was unwound and electrophoresed in an alkaline solution (300 mM NaOH, 1 mM EDTA, pH 13) for 20 minutes at 25 V and 300 mA (0.5–1 V/cm). The slides were then neutralised using 0.4 M Tris buffer (pH 7.5), and the gels were stained with GelRed. Images were captured and analysed using an Eclipse 800 fluorescence microscope (Nikon, Japan) equipped with a Basler camera and the Comet IV image analysis software (Perceptive Instruments, UK). Three independent experiments were conducted, with 50 randomly selected nuclei analysed per experimental condition. Results were expressed as the percentage of tail DNA.
Ključne besede: nanomaterials, graphene quantum dots, HepG2 spheroids, toxicity
Objavljeno v DiRROS: 31.07.2026; Ogledov: 114; Prenosov: 80
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Povzetek: Various types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment. Results Clinical presentation of toxicities of new anticancer therapies may be unpredictable and nonspecific. They can mimic other more common medical conditions such as infection or stroke. If not recognized and properly treated these toxicities can progress rapidly into life-threatening conditions. ICIs can cause immune-related inflammatory disorders of various organ systems (e.g. pneumonitis or colitis), and a cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may develop after treatment with CAR T-cells or BiTEs. The cornerstones of management of these hyper-inflammatory disorders are supportive care and systemic immunosuppressive therapy. The latter should start as soon as symptoms are mild-moderate. Similarly, some severe toxicities of ADCs also require immunosuppressive therapy. A multidisciplinary team including an oncologist/haematologist and a corresponding organ-site specialist (e.g. gastroenterologist in the case of colitis) should be involved in the diagnosis and treatment of these toxicities. Conclusions Health professionals should be aware of potential serious complications of new systemic anticancer therapies. Early diagnosis and treatment with adequate supportive care and immunosuppressive therapy are crucial for the optimal outcome of patients with these complications.
Ključne besede: potentially fatal toxicity, immune checkpoint inhibitors, immunosuppressive therapy
Objavljeno v DiRROS: 26.06.2026; Ogledov: 169; Prenosov: 76
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Povzetek: In the present study, two types of graphene quantum dots (GQDs) were investigated: green-emitting (G-GQDs) and blue-emitting (B-GQDs). Physicochemical characterisation was performed using transmission electron microscopy (TEM), zeta potential, and hydrodynamic radius measurements to evaluate the morphology, particle size, aggregation behaviour, and colloidal stability of the GQDs in both water and cell culture medium. G-GQDs exhibited superior colloidal stability and more uniform dispersion than B-GQDs, whereas both types showed reduced aggregation and surface charge in cell culture medium due to protein corona formation. Toxicological characterisation was performed using an in vitro human hepatocellular carcinoma (HepG2) 3D spheroid model, with GQDs exposures up to 250 µg/mL (100 µg/cm2). Cytotoxicity was measured using the CellTiter-Glo luminometric assay, while genotoxicity was evaluated by the comet assay and flow cytometric analysis of γH2AX and phosphorylated histone H3 (p-H3) after 24 h of exposure. Both GQDs induced dose-dependent cytotoxic effects in HepG2 spheroids. At non-cytotoxic concentrations, a dose-dependent increase in DNA damage was observed, as determined by the comet assay. However, no evidence of DNA double-strand breaks (γH2AX) or elevated p-H3 levels was detected, suggesting the absence of clastogenic and aneugenic activity. The observed DNA single-strand breaks may be partly attributed to reactive oxygen species induction. These results indicate that, although GQDs induced cytotoxicity and single-strand DNA damage, no clear evidence of more severe genotoxic effects was observed under the tested conditions. Further studies are warranted to elucidate underlying mechanisms and comprehensively assess the safety profile of GQDs for biomedical applications.
Ključne besede: nanomaterials, graphene quantum dots, HepG2 spheroids, toxicity
Objavljeno v DiRROS: 19.03.2026; Ogledov: 518; Prenosov: 192
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Povzetek: A recent study has suggested that plastics may contain more than 16,000 chemicals, including additives, processing aids, starting substances, intermediates and Non-Intentionally Added Substances. Plastic chemicals are released throughout the plastic life cycle, from production, use, disposal and recycling. Most of these chemicals have not been studied for potential hazardous properties for humans and in the environment. To refine the risk assessment of these leachable chemicals, additional hazard data are needed. The PlasticLeach project within the EU co-funded Partnership for the Assessment of Risks from Chemicals (PARC) aims to address this data gap by screening several plastic products in daily use. Leachates will be prepared from a number of these plastic items, and these chemical mixtures will be further tested using several test guideline compliant assays and New Approach Methodologies covering both human health and environmental endpoints. The most toxic leachates will be characterized using a non-targeted analysis pipeline to identify chemicals in the leachate. When single chemicals of concern are identified, these will be further tested to determine hazardous properties and identify the respective potency factors to better understand their specific hazard profiles. A tiered approach for hazard testing will be followed. The experimental work will be complemented by in silico toxicological profiling, using publicly available toxicity databases and tools, including Artificial Intelligence tools that cover both human and environmental endpoints. A comprehensive array of endpoints, including cytotoxicity, endocrine disruption, genotoxicity, immunotoxicity, reproductive toxicity and effects related to ecotoxicity will be evaluated. In this paper, we outline the plastic products to be tested and the battery of assays that will be used to identify hazards relevant to both human health and the environment. Data generated from in silico, in vitro, and in vivo approaches will be reported using standardized formats, stored within a centralized repository, and harmonized to adhere to the FAIR data principles (Findable, Accessible, Interoperable, and Reusable). This integrated strategy will not only advance our understanding of the risks associated with plastic-derived chemicals but will also provide critical support for regulatory decision-making and facilitate the development of safer, and more ecofriendly plastic materials in the future.
Ključne besede: plastics, chemicals, leachables, PARC, new approach methodologies, hazard assessment, toxicity, risk assessment
Objavljeno v DiRROS: 19.12.2025; Ogledov: 510; Prenosov: 373
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Povzetek: As a result of improper management, plastics such as drinking cups are accumulating in environmental compartments worldwide, impacting biodiversity and ecosystem services. The goal of this study is to analyze and compare potential environmental impacts of disposable cups made of Polypropylene and Polylactic acid with the help of a cradle-to-grave life cycle assessment, including impacts related to the littering of these cups. Plastic pollution impacts are calculated based on the products' persistence in the environment, comparing the results of our own experiment to literature data. As an indication of the possible adverse health effects of Polypropylene and Polylactic acid, a toxicity test of the chemical mixtures migrating from the cups is conducted. Overall, the cups made of Polypropylene show lower environmental impacts compared to those made of Polylactic acid when the experimentally determined degradation rates are used. Nevertheless, regarding toxicity of the chemical migrates, the cup made of Polylactic acid performs better than the one made of Polypropylene. Considering all impact categories, there is no overall improvement in environmental impacts of producing the cup from Polylactic acid instead of Polypropylene. Our results indicate the importance of using degradation data measured specifically for the assessed product. Methodologically, we demonstrate a possible integration of life cycle assessment and safe-and-sustainable-by-design scoring. Further development of the plastic pollution impact category is needed to integrate effects on the terrestrial environment.
Ključne besede: degradation, accelerated weathering, product environmental footprint, life cycle assessment, plastic pollution, toxicity
Objavljeno v DiRROS: 27.05.2025; Ogledov: 1502; Prenosov: 991
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