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Search Results (253)

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Keywords = Cu(II) toxicity

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34 pages, 4853 KB  
Review
GHK-Cu as a Bioactive Metallopeptide and Drug-Delivery Cargo: Coordination Chemistry, Formulation Science, Therapeutic Evidence, and a Translational Roadmap
by Diana-Maria Mateescu, Dragos-Mihai Gavrilescu, Ruxandra-Ioana Mincioaga, Ana-Maria Pah, Ana-Olivia Toma, Daniela-Vasilica Serban, Cristiana Adina Avram, Maria-Laura Craciun, Bogdan Enache and Camelia-Oana Muresan
Pharmaceutics 2026, 18(9), 1077; https://doi.org/10.3390/pharmaceutics18091077 - 27 Aug 2026
Viewed by 381
Abstract
Background/Objectives: Glycyl-L-histidyl-L-lysine (GHK) and its copper(II) complex GHK-Cu have been studied for matrix remodeling, inflammation, redox regulation, angiogenesis, and tissue repair, yet the literature frequently treats GHK-Cu as a single active ingredient despite formulation-dependent variation in coordination state, speciation, stability, pharmacokinetics, and [...] Read more.
Background/Objectives: Glycyl-L-histidyl-L-lysine (GHK) and its copper(II) complex GHK-Cu have been studied for matrix remodeling, inflammation, redox regulation, angiogenesis, and tissue repair, yet the literature frequently treats GHK-Cu as a single active ingredient despite formulation-dependent variation in coordination state, speciation, stability, pharmacokinetics, and toxicity. We critically evaluate GHK-Cu simultaneously as a bioactive metallopeptide and as a drug-delivery cargo, with explicit separation of apo-GHK, canonical GHK-Cu, GHK-derived copper peptides, and non-GHK copper-peptide systems. Methods: We conducted a structured systematic evidence-mapping review of PubMed/MEDLINE, Europe PMC, major publisher platforms, ClinicalTrials.gov, backward citation chains, and official European Union, U.S., and ICH regulatory sources from database inception through 12 August 2026. Biological evidence level and chemical/formulation quality were graded independently using an author-defined two-axis framework. Delivery studies were extracted against a fixed matrix comprising formulation, claimed loading, molar copper occupancy, labile copper, species-resolved release, factorial controls, stability/manufacturability, and objective outcome. Quantitative pooling was not performed because active-entity definitions, formulations, doses, models, comparators, and endpoints were not quantitatively commensurable. Results: Preclinical data consistently support effects on matrix remodeling, epithelial repair, inflammatory/redox regulation, and angiogenesis, but the clinical evidence remains sparse and does not meet contemporary active-entity quality standards. Historical cosmetic reports are small or incompletely characterized; a 13-participant post-CO2-laser study was negative on objective endpoints, whereas a 2026 18-participant split-face eyebrow study reported positive cosmetic hair outcomes but did not define GHK-Cu speciation or local exposure. The ongoing phase 2 acute-wound study NCT07437586 remains recruiting and has no efficacy results; its registration cannot be used as evidence of clinical translation. Across delivery studies, particle size, polydispersity, encapsulation efficiency, total peptide/copper content, and bulk release are often reported, whereas molar occupancy, labile copper, and release of intact GHK-Cu versus apo-GHK/free copper are usually not resolved. Conclusions: Translation is limited less by biological plausibility than by pharmaceutical definition and evidence attribution. We define the “active pharmaceutical entity” operationally as the reproducible chemical state intended to mediate pharmacology at administration, not as an established regulatory designation or a claim that one immutable molecular species persists in biological fluids. We further propose, explicitly as an author-derived development framework rather than a consensus standard, a control strategy based on molar occupancy, route-specific labile copper specifications, orthogonal speciation, mechanism-linked potency, species-resolved release, factorial controls, route-specific safety decision thresholds, ICH-aligned stability, and GMP-scalable manufacture. Until these requirements are met and controlled clinical efficacy is demonstrated, GHK-Cu should be regarded as a promising but unproven therapeutic cargo rather than a clinically validated regenerative drug. Full article
(This article belongs to the Special Issue Peptide-Based Drug Delivery Systems: From Design to Application)
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26 pages, 7430 KB  
Review
A Review of Recent Advances in Conversion and Self-Assembled Anti-Corrosion Films for Copper and Its Alloys
by Kangwei Gongsun, Xiang Gao, Changfeng Zhao and Houyi Ma
Molecules 2026, 31(16), 2869; https://doi.org/10.3390/molecules31162869 - 17 Aug 2026
Viewed by 206
Abstract
Copper and its alloys are indispensable for electronics, communications, new energy systems, and aerospace engineering due to their exceptional electrical conductivity and mechanical properties. However, the thin cuprous oxide (Cu2O) layer that naturally forms on copper and its alloys is prone [...] Read more.
Copper and its alloys are indispensable for electronics, communications, new energy systems, and aerospace engineering due to their exceptional electrical conductivity and mechanical properties. However, the thin cuprous oxide (Cu2O) layer that naturally forms on copper and its alloys is prone to failure under elevated temperatures and high humidity, particularly in chloride-rich environments, leading to accelerated localized corrosion. While conventional chromate-based passivation has long been the industrial standard for preventing corrosion, its use has been increasingly restricted by global regulations (such as RoHS and REACH) due to its severe toxicity and health risks. To address the conflict between environmental compliance and protective performance, this review systematically evaluates recent advances in environmentally friendly, chromium-free anti-corrosion coatings in the present review. These alternative coatings are critically analyzed and categorized into four mechanistic groups: (i) inorganic conversion coatings (including molybdate, tungstate, rare earth, and phosphate systems); (ii) organic films formed via chemical or physical adsorption (such as organic inhibitors, thiol-based monolayers, and organosilane self-assembled films); (iii) conversion coatings engineered through covalent bonding, coordination chemistry, and microstructural tailoring; and (iv) multifunctional coatings that integrate self-healing capability with high electrical conductivity. Beyond providing a technical summary, this review explored how the swift progression of electronic information technology, new energy infrastructure, and robotics has imposed more exacting, multifunctional demands on copper components. This review provides a strategic roadmap for future research and prioritizes the creation of protection strategies that operate robustly in multi-physics coupling environments—integrating high conductivity, autonomous self-healing, and long-term chemical stability to ensure the reliability of next-generation infrastructure. Full article
(This article belongs to the Special Issue Advancements in Electrochemistry and Corrosion Protection)
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21 pages, 2073 KB  
Article
Cyclodextrin Polymer-Supported Cu-Fe Nanoparticles Enhanced the Degradation of 4-Chlorophenol by Citric Acid Complexation
by Hao Liu, Deli Wu, Yufan Chen, Chengsi Hou, Guojie Ye, Zhengwei Zhou and Yue Wang
Sustainability 2026, 18(16), 8079; https://doi.org/10.3390/su18168079 - 7 Aug 2026
Viewed by 323
Abstract
4-Chlorophenol (4-CP) is a persistent and highly toxic pollutant commonly found in groundwater. However, its efficient degradation remains challenging due to the rapid agglomeration of conventional zero-valent iron (ZVI) nanoparticles, their narrow pH operating range, and the environmental risks associated with synthetic chelating [...] Read more.
4-Chlorophenol (4-CP) is a persistent and highly toxic pollutant commonly found in groundwater. However, its efficient degradation remains challenging due to the rapid agglomeration of conventional zero-valent iron (ZVI) nanoparticles, their narrow pH operating range, and the environmental risks associated with synthetic chelating agents. To address these limitations, this study presents a rationally designed catalytic system integrating cyclodextrin polymer (CDP)-supported bimetallic Cu-Fe nanoparticles (Cu-Fe-CDP) with citric acid (CA) as a green complexing agent. The porous CDP matrix effectively mitigates nanoparticle agglomeration and provides abundant active sites, while the Fe-Cu bimetallic coupling accelerates electron transfer and iron corrosion. Critically, CA acts as a biocompatible ligand that sustains Fe(II)/Fe(III) redox cycling, expands the effective pH range, and enhances hydroxyl radical (·OH) generation. The system achieves 92.13% degradation of 4-CP within 80 min at pH 9.0 and nearly complete removal at pH values between 3.0 and 7.0. Mechanistic studies, including electron paramagnetic resonance (EPR) spectroscopy and radical quenching tests, confirm the dominance of ·OH radicals (82.67% inhibition by TBA) and the essential role of surface Fe(II)/Fe(III) cycling. The catalyst exhibits excellent reusability, broad-spectrum activity toward multiple pollutants, and sustained performance in real water matrices and long-term column tests with minimal metal leaching. This work demonstrates a chemically robust strategy for chlorophenol remediation using green citric acid and biodegradable CDP without exogenous oxidant addition, showing promise for further development toward practical applications. Full article
(This article belongs to the Section Soil Conservation and Sustainability)
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39 pages, 28686 KB  
Article
Investigations of the Molecular Nature of Low-Molecular-Mass Copper(II) Ion Complexes in Human Saliva: Physiological and Toxicological Significance
by Kayleigh Hunwin, Oliver Megram, Georgina Page, Wyman Chan, Nazmin Juma, Rachel Armitage, Olivia Steel, Katie Jane Hewitt and Martin Grootveld
Molecules 2026, 31(15), 2686; https://doi.org/10.3390/molecules31152686 - 1 Aug 2026
Viewed by 394
Abstract
Copper is an essential trace element that plays critical roles in enzymatic processes and cellular metabolism. However, excessive exposure to its ions can lead to toxicity through oxidative stress mechanisms. Therefore, the chemical ‘speciation’ of copper(II) ions (Cu(II)) in biological fluids such as [...] Read more.
Copper is an essential trace element that plays critical roles in enzymatic processes and cellular metabolism. However, excessive exposure to its ions can lead to toxicity through oxidative stress mechanisms. Therefore, the chemical ‘speciation’ of copper(II) ions (Cu(II)) in biological fluids such as saliva is of critical importance. However, currently this phenomenon remains poorly understood, despite its importance for our understanding of bioavailability, toxicity, and sensory perception. Therefore, this study employed 1H nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy, and scanning electron microscopy (SEM) to investigate the molecular nature and complexation characteristics of low-molecular-mass Cu(II) complexes formed in human whole mouth salivary supernatant (WMSS) samples. Findings obtained revealed that Cu(II) ions form distinct complexes with salivary biomolecules, particularly amino acids such as histidine and glutamine, aromatic metabolites, proteins, and further small organic biomolecules, e.g., carboxylic acid anions. These results provide new insights into copper speciation in the oral cavity, with implications for dietary Cu(II) ion availability, metallic taste perception, and potential toxicological risks associated with elevated oral exposure levels. Full article
(This article belongs to the Special Issue NMR and MRI in Materials Analysis: Opportunities and Challenges)
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18 pages, 1417 KB  
Article
Click Chemistry Approach to Derivatisation of Fluconazole
by Michał Janowski, Oleg M. Demchuk, Sylwia Andrzejczuk, Angelika Pawlicka, Urszula Kosikowska, Marta Struga, Marcin Feldo and Monika Wujec
Molecules 2026, 31(14), 2545; https://doi.org/10.3390/molecules31142545 - 22 Jul 2026
Viewed by 494
Abstract
The emergence of antimicrobial resistance necessitates the development of structurally novel agents with improved biological profiles. In this study, a series of new derivatives of fluconazole were designed, synthesized, and evaluated for antifungal activity. The synthetic approach involved esterification of hydroxyl group of [...] Read more.
The emergence of antimicrobial resistance necessitates the development of structurally novel agents with improved biological profiles. In this study, a series of new derivatives of fluconazole were designed, synthesized, and evaluated for antifungal activity. The synthetic approach involved esterification of hydroxyl group of fluconazole with an azide-group-containing benzoyl chloride, followed by copper-catalyzed azide–alkyne cycloaddition (CuAAC). The optimized catalytic system was based on a copper(I) catalyst generated from copper(II) palmitate and ascorbic acid. The transformations of the azide-containing derivatives were then performed. The obtained compounds were tested against reference strains of clinically relevant Candida spp., including C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 14243, C. auris CDC B11903, C. tropicalis ATCC 1369, C. glabrata ATCC 15126, and C. lusitaniae ATCC 3449. Some of the obtained derivatives showed very low toxicity in the MTT-based cell viability assay while maintaining high antifungal activity against selected strains. Full article
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27 pages, 6931 KB  
Article
Complex Distribution Phenomena and Plastic Binding of Test Chemicals in Cell Culture Experiments: Exemplification by Tebufenpyrad
by Mahshid Alimohammadi, Hiba Khalidi, Elias Zgheib, Anna-Katharina Holzer, Naja Bürgers, Céline Brochot, Patrik Lundquist, Viktoria Magel, Baiba Gukalova, Edgars Liepinsh and Marcel Leist
Int. J. Mol. Sci. 2026, 27(12), 5547; https://doi.org/10.3390/ijms27125547 - 19 Jun 2026
Viewed by 599
Abstract
Biokinetic complexities (plastic sorption, protein binding, and cellular accumulation) may cause large discrepancies between nominal and biologically effective concentrations of test compounds assessed by new approach methods (NAMs). This case study was performed to explore a generally applicable workflow that addresses biokinetic complexities [...] Read more.
Biokinetic complexities (plastic sorption, protein binding, and cellular accumulation) may cause large discrepancies between nominal and biologically effective concentrations of test compounds assessed by new approach methods (NAMs). This case study was performed to explore a generally applicable workflow that addresses biokinetic complexities in the context of NAM-based hazard testing for next-generation risk assessment (NGRA). The pesticide tebufenpyrad (TEBU) is a challenging test compound, as it (i) is hydrophobic, (ii) has an intracellular target (mitochondrial respiration), and (iii) is acting at low concentrations (susceptible to biokinetic complexities). In the newly established NeuriTox-M neurotoxicity assay, based on human dopaminergic (LUHMES) neuron cultures, TEBU showed toxic effects at 20 nM. Mass spectrometric analyses of various experimental setups showed that a large fraction (75% to >90%) of TEBU was adsorbed to plastic. This effect was strongly attenuated by albumin in the medium. Cells, cultured on plastic, were considered unsuitable to assess cellular uptake. Therefore, alternatives were explored: when cells were used as suspension cultures (3% v/v) in albumin-containing medium, analysis worked best. Under such conditions, the concentration ratio (cells/medium) of TEBU was around 10. Data from an in vitro distribution (VIVD) model were in good agreement with the measurements. VIVD predicted the unbound medium TEBU concentration (Cu) to be 2–3 orders of magnitude below the nominal concentration and the total cellular concentration to be 10–100-fold above. Standard cell culture assays showed that the medium albumin content indeed altered the TEBU toxicity threshold. More such studies are needed to embed biokinetics information into NGRA. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Pesticide Toxicity and Action)
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27 pages, 3242 KB  
Article
Deciphering the Antioxidant Activity and Enzyme Inhibition of Luteolin and Its Glycosides: An Integrated In Vitro and In Silico Approach
by Adem Ertürk and Ilhami Gulcin
Catalysts 2026, 16(6), 550; https://doi.org/10.3390/catal16060550 - 14 Jun 2026
Viewed by 750
Abstract
Luteolin and its derivative glycosides (cynaroside, orientin and isoorientin) are compounds with a flavonoid structure of plant origin. There are different studies in the literature on the antioxidant capacities of the structures and their inhibition effects on some enzymes. In this study, the [...] Read more.
Luteolin and its derivative glycosides (cynaroside, orientin and isoorientin) are compounds with a flavonoid structure of plant origin. There are different studies in the literature on the antioxidant capacities of the structures and their inhibition effects on some enzymes. In this study, the antioxidant capacities of each structure were determined comparatively, and their inhibitory effects against enzymes associated with different diseases such as acetylcholinesterase, butyrylcholinesterase, α-glycosidase and α-amylase were evaluated by comparative investigation in vitro and in silico. Antioxidant capacities were determined for each structure by iron ions (Fe3+), cupric ions (Cu2+), Fe3+−Triphenyltetrazolium chloride (TPTZ) reduction methods and 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), N,N-dimethyl-p-phenylenediamine (DMPD) radical scavenging methods. According to the results obtained, it was determined that the antioxidant capacities of the structures were close to or better than butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), trolox, α tocopherol and ascorbic acid, which are used as standard antioxidants. The results of the study, which was conducted to determine the inhibition effects of the structures on the determined enzymes, were found to coincide experimentally and theoretically. According to the inhibition results, the best inhibitors were found as orientin (IC50: 27.729 nM) for the human carbonic anhydrase I (hCA I), cynaroside (IC50: 18.24 nM) for the human carbonic anhydrase I (hCA II), isoorientin (IC50: 1.93 nM) for the acetylcholinesterase (AChE), and cynaroside (IC50: 6.41 and 7.15 nM) for the butyrylcholinesterase (BChE) and α-glycosidase enzymes. Additionally, absorption, distribution, metabolism, and excretion (ADME) profiles and toxicity assessments of the structures were determined in a virtual environment. Full article
(This article belongs to the Special Issue Enzyme Engineering—the Core of Biocatalysis)
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32 pages, 2227 KB  
Review
Potential Activity of Non-Platinum Metal-Based Organic Complexes Against Different Cancer Cell Types
by Dobrina Tsvetkova, Stefka Ivanova and Danka Obreshkova
Pharmaceuticals 2026, 19(6), 925; https://doi.org/10.3390/ph19060925 - 12 Jun 2026
Cited by 1 | Viewed by 828
Abstract
The disadvantages of Cisplatin in anticancer treatment are connected to its poor selectivity, resistance developed of cancers to the drug, and its toxicity against normal organs. An important strategy in anticancer treatment is the synthesis and clinical investigation of non-platinum metal complexes with [...] Read more.
The disadvantages of Cisplatin in anticancer treatment are connected to its poor selectivity, resistance developed of cancers to the drug, and its toxicity against normal organs. An important strategy in anticancer treatment is the synthesis and clinical investigation of non-platinum metal complexes with superior anticancer activity and improved selectivity compared to Cisplatin, combined with lower toxicity, fewer side effects and decreased resistance of cancer to the drug. In the current study, we aim to summarize the potential of important non-platinum metal-based organic compounds as therapeutic agents against different cancer cell types. The review covers the general principles of chemotherapy. A literature analysis shows that organic complexes of the metalloids arsenic (As), boron (B), antimony (Sb), and selenium (Se), and of metals, such as Ag, Au, Co, Cu, Fe, Mn, Mo, Ni, Zn, Ce, Ga, Gd, Ir, Os, Pd, Re, Rh, Ru, Ti, and V, have been investigated for potential applications in cancer therapy. This is due to their antiproliferative effects against different cancer types: lung [Cd(II), Co(II), Cu(II), Ni(II), Mn(II), Ru(II), Zn(II)]; breast [Ag(I), Cu(I), Cu(II), Ir(III), Ni(II), Mn(II),. Rh(III), Ru(II)]; gastric [Cu(II), Cu(II)-La(III)]; colon [Ag(I), Cu(II), Ir(III), Pd(II), Rh(III), Ru(II), vanadium(V)]; colorectal [Ag(I), Co(II), Cu(II), Zn(II)]; liver [Ag(I), Co(II), Cu(II), Gd(III), vanadium(V)]; pancreatic [vanadium(IV)]; bladder [Ag(I), Cu(II), Ru(II)]; cervical [Ag(I), Au(I), Cu(I), Cu(II), Fe(II), Ir(III), Rh(III), Ru(II)]; testicular [vanadium(IV)]; prostate [Cu(II), Pd(II), Zn(II)]; leukemia [Ag(I), Co(II), Cu(II), Pd(II), Zn(II)]; sarcoma [Co(II), Ni(II), Zn(II)]; mesothelioma [Cu(II)]; neuroblastoma [Cu(II)]; glioma [Cu(II)]; and melanoma [Au(I), Cu(II), Pd(II), Ru(II)]. The main goals for increasing anticancer metal-based complexes include increasing anticancer activity and selectivity, reducing toxicity, and avoiding cancer cell resistance. Compared to Cisplatin, organocomplexes of copper, ferrocene, and ruthenium are more active. Ruthenium and copper complexes, in particular, are also more selective. Notably, ruthenium and ferrocene derivatives are less toxic than Cisplatin. Lastly, cancers appear to exhibit less resistance against copper, gold, ruthenium, palladium, and ferrocene complexes. Full article
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20 pages, 921 KB  
Article
Synthesis and Antitumor Activity of Metallates Incorporating Functionalized Azolium Salts
by Tommaso Lorenzon, Alessia Schiavo, Anita Piccoli, Nicolò Perin, Lorenzo Rodighiero, Nicola Demitri, Giovanni Tonon, Fabiano Visentin, Flavio Rizzolio, Isabella Caligiuri, Martina Scianna, Catherine S. J. Cazin, Steven P. Nolan and Thomas Scattolin
Inorganics 2026, 14(6), 155; https://doi.org/10.3390/inorganics14060155 - 7 Jun 2026
Viewed by 1141
Abstract
Azolium-derived metallates are well-established intermediates in metal–N-heterocyclic carbene chemistry; however, their potential as standalone therapeutic agents remains largely unexplored. Herein, we report the first systematic biological investigation of a diverse family of Au(I), Cu(I), Pt(II), Pd(II), and Ru(II) metallates paired with [...] Read more.
Azolium-derived metallates are well-established intermediates in metal–N-heterocyclic carbene chemistry; however, their potential as standalone therapeutic agents remains largely unexplored. Herein, we report the first systematic biological investigation of a diverse family of Au(I), Cu(I), Pt(II), Pd(II), and Ru(II) metallates paired with functionalized azolium cations. The complexes were synthesized quantitatively through a simple, atom-economical, and purification-free protocol under aerobic conditions in technical-grade green solvents. Structural characterization by multinuclear NMR spectroscopy and single-crystal X-ray diffraction confirmed metallate formation and enabled the first isolation and crystallographic characterization of unprecedented azolium-derived ruthenates. The antiproliferative activity of the complexes was evaluated against cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines, alongside non-cancerous MRC-5 fibroblasts. Backbone-functionalized derivatives emerged as the most potent compounds, displaying activities comparable or superior to cisplatin in A2780 cells and up to 1000-fold higher potency in the resistant A2780cis model. Notably, unlike cisplatin, the metallates retained nearly unchanged IC50 values across both ovarian cancer lines, strongly suggesting resistance-evasive mechanisms of action. While benzylazido- and methyl guanosine-derived complexes generally exhibited lower overall potency, several members retained significant activity in resistant cells while showing markedly reduced toxicity toward normal fibroblasts, highlighting promising selectivity profiles. Ethoxide-functionalized derivatives and platinum-based metallates combined pronounced anticancer activity with favourable therapeutic windows. Overall, this work establishes azolium-derived metallates as a previously overlooked class of metal-based anticancer agents combining exceptional synthetic accessibility, broad structural tunability, and remarkable activity against platinum-resistant ovarian cancer. Full article
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18 pages, 5465 KB  
Article
Enhanced Removal of Copper Ions from Aqueous Solution by Citrate-Stabilized Amorphous Calcium Phosphate Nanoparticles/Sodium Alginate Composite Hydrogel Beads
by Miaomiao Wang, Yuwei Jiang and Junjun Tan
Nanomaterials 2026, 16(11), 662; https://doi.org/10.3390/nano16110662 - 24 May 2026
Viewed by 562
Abstract
Although amorphous calcium phosphate (ACP) has been extensively employed as a biomaterial in dental and orthopedic fields, its exploration for environmental applications—particularly in potentially toxic element remediation—remains notably limited in the scientific literature. This study reports the rational design of a multifunctional adsorbent [...] Read more.
Although amorphous calcium phosphate (ACP) has been extensively employed as a biomaterial in dental and orthopedic fields, its exploration for environmental applications—particularly in potentially toxic element remediation—remains notably limited in the scientific literature. This study reports the rational design of a multifunctional adsorbent by integrating sodium citrate-stabilized ACP (Cit-ACP) nanoparticles into calcium-crosslinked sodium alginate (SA) hydrogel beads for selective Cu2+ sequestration from aqueous systems. Comprehensive sorption assessments revealed that equilibrium uptake aligned with the Freundlich isotherm (indicating heterogeneous surface interactions), while kinetic profiles adhered to pseudo-second-order behavior, characteristic of chemisorption-driven processes. Under optimized operational parameters (pH 5.0, 45 °C), the Cit-ACP/SA composite attained an exceptional maximum adsorption amount of 307.76 mg/g. Thermodynamic analysis further confirmed the spontaneity (ΔG° < 0) and endothermic nature (ΔH° > 0) of the process. Multi-technique characterization (XPS, FTIR, XRD, pH trajectory) elucidated a dual-mode adsorption mechanism: (i) ion exchange between aqueous Cu2+ and structural Ca2+ within both the alginate matrix and ACP framework; and (ii) in situ surface precipitation yielding copper-substituted hydroxyapatite. Owing to its facile aqueous-phase synthesis, superior adsorption performance, biodegradability, macroscopic bead morphology enabling rapid separation, and robust selectivity in complex matrices, the Cit-ACP/SA composite presents a sustainable, scalable, and eco-compatible platform for practical remediation of copper-contaminated wastewater. Full article
(This article belongs to the Section Environmental Nanoscience and Nanotechnology)
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21 pages, 2915 KB  
Article
Tissue-Specific Accumulation and Dietary Risk of Arsenic and Other Potentially Toxic Elements in Retail Meats
by Syed Sayyam Abbas, Syed Ali Musstjab Akber Shah Eqani, Ismat Nawaz, Mansoor A. Alghamdi, Ahmed S. Summan, Abdul Qadir, Shabbar Abbas, Iqra Rasheed, Syeda Maria Ali, Mustafa Nawaz Shafqat, Mohammed I. Orif, Heqing Shen and Nadeem Ali
J. Xenobiotics 2026, 16(3), 90; https://doi.org/10.3390/jox16030090 - 21 May 2026
Viewed by 1360
Abstract
Data on arsenic (As) and other potentially toxic elements (PTEs) in Pakistani retail meats are limited, constraining evidence-based dietary risk assessment and management. This study aimed to determine the concentrations and profiles of As and seven other PTEs (Cr, Ni, Mn, Pb, Cd, [...] Read more.
Data on arsenic (As) and other potentially toxic elements (PTEs) in Pakistani retail meats are limited, constraining evidence-based dietary risk assessment and management. This study aimed to determine the concentrations and profiles of As and seven other PTEs (Cr, Ni, Mn, Pb, Cd, Cu, Zn) in commonly consumed meats and to evaluate the associated non-carcinogenic health risks. Ninety-two paired liver and muscle samples from broiler chicken, goat (mutton), and beef cattle were collected from four cities across the Indus Plain and analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Dietary exposure was evaluated using estimated daily intake (EDI), target hazard quotient (THQ), and hazardous index (HI) under typical and high-consumption scenarios. Overall, Zn and Cu exhibited the highest concentrations, followed by Mn and Cr, whereas As, Pb, Ni, and Cd occurred at comparatively lower but environmentally relevant levels. Beef liver exhibited the highest contamination levels, exceeding FAO/WHO permissible limits for Pb, Cu, and Cd in up to 40% of samples. In contrast, mutton and beef muscle contained the highest As and Zn concentrations, while chicken muscle showed elevated Cr levels. Multivariate statistical analysis revealed three dominant co-variation patterns, suggesting potential contamination pathways: (i) geogenic groundwater sources enriched with As, Cr, and Ni; (ii) atmospheric and industrial dust inputs linked with Pb, Cd, and Mn; (iii) mineral-enriched feed additives potentially contributing to elevated Zn and Cu, particularly in poultry. Under high-consumption scenarios, THQ values for As, Cr, Cu, and Zn exceeded the safety threshold (THQ > 1), highlighting beef products as the dominant source of chronic dietary risk. Overall, the findings highlight pronounced tissue- and species-specific accumulation trends, and emphasizes the urgent need for stricter feed and water quality control measures to minimize dietary exposure to PTEs. Full article
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25 pages, 3307 KB  
Article
Transcriptomic Profiling of Toxic Copper Overload Induced by CuO Nanoparticles or Copper Ions in Human Lung Epithelial and Liver Cells
by Jana Kuhn, Anda R. Gliga, Cheyenne Ines Aissouni, Anna Maria Glowacki, Marlene Parsdorfer, Martin Link, Hanna Lovisa Karlsson and Andrea Hartwig
Nanomaterials 2026, 16(10), 590; https://doi.org/10.3390/nano16100590 - 12 May 2026
Viewed by 776
Abstract
The transition metal copper (Cu) is an essential trace element for humans and serves as a cofactor for numerous enzymes. Therefore, intracellular Cu homeostasis must be tightly regulated. Meanwhile, Cu is increasingly used in industrial and biomedical applications, particularly in nanoparticle (NP) form. [...] Read more.
The transition metal copper (Cu) is an essential trace element for humans and serves as a cofactor for numerous enzymes. Therefore, intracellular Cu homeostasis must be tightly regulated. Meanwhile, Cu is increasingly used in industrial and biomedical applications, particularly in nanoparticle (NP) form. However, studies have demonstrated that Cu(II) oxide (CuO) NPs are highly toxic. Therefore, understanding the underlying toxic effects of such compounds is of the utmost importance. In this context, transcriptomic profiling is regarded as a valuable tool. Nevertheless, comparative studies addressing organ-relevant models, such as the liver and lungs, are scarce. Furthermore, no transcriptomic studies have been conducted on human bronchial lung epithelial cells exposed to CuO NPs and Cu2+. In this study, we compared the cellular effects of human bronchial lung epithelial cells exposed to both CuO NPs and Cu2+ to the effects in human liver cells exposed to Cu2+ by applying RNA sequencing. Although cytotoxicity was comparable, we showed that Cu uptake was highly dependent on both the cell type and the form of Cu. The most pronounced concentration-dependent transcriptional changes were observed with CuO NP exposure in BEAS-2B cells. The only differentially expressed genes (DEGs) found by all exposures and treatments were metallothioneins (MTs). The most sensitive targets of Cu-induced toxicity were related to nuclear factor erythroid 2-related factor 2 (NRF2), nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), and mitogen-activated protein kinase (MAPK) signaling. Furthermore, the effects observed at the transcriptome level were studied at the functional level, such as cell cycle regulation and cytokine release. Thus, we demonstrated that the two cell types differ in susceptibility, and that complementing transcriptome profiling with functional studies provides important mechanistic insights. Full article
(This article belongs to the Special Issue Nanotoxicology: Small Particles, Big Concerns)
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24 pages, 7475 KB  
Review
Cellulose-Based Composite Hydrogels for Heavy Metal Ion Removal: Recent Advances and Engineering Perspectives
by Xiaobo Xue, Jihang Hu, Panrong Guo, Liyun Wang, Luohui Wang, Youming Dong, Fei Xiao, Cheng Li and Shen Ding
Gels 2026, 12(5), 380; https://doi.org/10.3390/gels12050380 - 30 Apr 2026
Cited by 9 | Viewed by 1539
Abstract
With the rapid intensification of industrial and agricultural activities, water contamination by heavy metal ions has emerged as a critical global challenge, gravely imperiling ecosystem stability and public health. Among the various remediation technologies, adsorption has been widely adopted due to its high [...] Read more.
With the rapid intensification of industrial and agricultural activities, water contamination by heavy metal ions has emerged as a critical global challenge, gravely imperiling ecosystem stability and public health. Among the various remediation technologies, adsorption has been widely adopted due to its high efficiency, low-cost water treatment, and simplicity of operation. However, conventional inorganic or synthetic adsorbents often exhibit poor degradability and pose a risk of secondary contamination, substantially limiting their sustainable application. Consequently, the development of environmentally benign and renewable adsorbent materials has become a central research focus in this field. Recently, cellulose-based composite hydrogels, derived from renewable resources and characterized by excellent eco-friendliness and highly tunable three-dimensional porous structures, have attracted considerable attention as promising green adsorption materials. These hydrogels demonstrate outstanding performance in the efficient sequestration of heavy metal contaminants from aqueous environments. This review systematically summarizes recent advances in cellulose-based composite hydrogels for heavy metal removal, to elucidate the structure–performance relationships linking material fabrication strategies, structural modulation, and adsorption efficiency. First, we outline the principal construction approaches, including physical crosslinking, chemical modification, and supramolecular self-assembly, and comprehensively analyze how different synthesis routes regulate pore architecture, mechanical properties, and the distribution of surface functional groups. Second, the underlying adsorption mechanisms, primarily coordination complexation, electrostatic interactions, and ion exchange, are discussed in detail. Finally, recent studies on the adsorption of cationic heavy metals (e.g., Pb(II), Cu(II), and Cd(II)) and anionic oxyanions (e.g., As(III) and Cr(VI)) are critically reviewed, with particular emphasis on the relationships between selective adsorption performance, material design principles, and specific recognition mechanisms. Overall, this review provides a theoretical foundation and practical guidance for the design and development of next-generation water treatment materials with high adsorption capacity, excellent selectivity, non-toxicity, and strong environmental compatibility, followed by future research recommendations. Full article
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24 pages, 20745 KB  
Article
pH-Responsive Bovine Serum Albumin Nanoparticles Encapsulating Doxorubicin-Based Complexes Induce Cuproptosis in Lung Cancer Cells
by Haiying Zhang, Xuanjia Chen, Shihui Qiao, Huanfeng Meng, Hui Long, Huamin Zhong, Yiheng Liu, Yun Song, Yanan Gao, Yan Liu and Lujia Mao
Pharmaceutics 2026, 18(5), 526; https://doi.org/10.3390/pharmaceutics18050526 - 26 Apr 2026
Viewed by 1107
Abstract
Background/Objectives: This study investigates the induction of cuproptosis in A549 lung cancer cells by doxorubicin (DOX) complexes and the development of pH-responsive bovine serum albumin (BSA)-based nanocarriers for their delivery. We successfully synthesized and characterized two novel complexes: DOX–Cu, where DOX acts [...] Read more.
Background/Objectives: This study investigates the induction of cuproptosis in A549 lung cancer cells by doxorubicin (DOX) complexes and the development of pH-responsive bovine serum albumin (BSA)-based nanocarriers for their delivery. We successfully synthesized and characterized two novel complexes: DOX–Cu, where DOX acts as a ligand for Cu(II), and DOX–BTZ, a conjugate formed between DOX and the proteasome inhibitor bortezomib (BTZ). Methods: Spectroscopic and NMR analyses were performed to confirm the formation of the complexes. In vitro assays were conducted to evaluate cytotoxicity in A549 cells, alongside assessment of DLAT aggregation as a marker of cuproptosis. The formulation of DOX into BSA nanoparticles (DOX–Cu@BSA NPs and DOX–BTZ@BSA NPs) was carried out to evaluate potential alleviation of DOX-induced cytotoxicity in cardiomyocytes in vitro. Fluorescence quenching and molecular docking studies were employed to investigate the binding interactions between the complexes and BSA. Cellular uptake experiments were performed to assess nanoparticle internalization into A549 cells. Results: Both complexes exhibited superior cytotoxicity against A549 cells compared to individual components. This enhanced cell death was associated with significant aggregation of dihydrolipoamide S-acetyltransferase (DLAT), a key marker of cuproptosis, suggesting the involvement of this copper-dependent cell death pathway. The BSA nanoparticles displayed favorable characteristics, including uniform size (~190 nm), high encapsulation efficiency (~75–79%), and colloidal stability. Crucially, they exhibited a pH-responsive drug release profile, with significantly accelerated release under acidic conditions (pH 5.7) mimicking the tumor microenvironment. Fluorescence quenching and molecular docking studies revealed strong, spontaneous binding between the complexes and BSA, primarily driven by hydrophobic interactions. Cellular uptake experiments confirmed efficient internalization of the nanoparticles into A549 cells. Conclusions: Collectively, this work offers a proof-of-concept for a strategy of utilizing BSA-based multidrug delivery systems for cuproptosis induction, offering a potential avenue to enhance therapeutic efficacy while reducing systemic toxicity in lung cancer treatment. Full article
(This article belongs to the Special Issue New Insights into Nanomaterials for Cancer Therapy and Drug Delivery)
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18 pages, 1907 KB  
Review
Chitosan-Based Adsorbents: A Versatile Platform for the Removal of Arsenate and Copper Ions from Water
by Lingli Min, Shuhua Wang, Yuling Li, Yiting Lin and Yulang Chi
Nanomaterials 2026, 16(8), 458; https://doi.org/10.3390/nano16080458 - 13 Apr 2026
Viewed by 716
Abstract
Chitosan, owing to its abundant amino and hydroxyl functional groups, serves as an effective biosorbent for the removal of toxic metal(loid) ions from water. This review summarizes recent advances in chitosan-based adsorbents specifically for arsenate (As(V)) and copper ions (Cu(II)), with an emphasis [...] Read more.
Chitosan, owing to its abundant amino and hydroxyl functional groups, serves as an effective biosorbent for the removal of toxic metal(loid) ions from water. This review summarizes recent advances in chitosan-based adsorbents specifically for arsenate (As(V)) and copper ions (Cu(II)), with an emphasis on adsorption mechanisms and electrospun nanofiber technologies. A conceptual “charge adaptation–structure synergy” model is proposed to elucidate the distinct adsorption behaviors of chitosan toward anionic and cationic substances: under acidic conditions, As(V) adsorption is dominated by electrostatic attraction to protonated amino groups, whereas at pH values near or above the pKa, Cu(II) removal proceeds via synergistic chelation involving deprotonated amino and hydroxyl groups. Competitive and synergistic interactions in binary systems, particularly between As(V) and coexisting anions such as phosphate, are also discussed. Notably, the kinetic advantages of electrospun chitosan nanofibers are highlighted, with equilibrium times shortened from several hours to approximately 0.5–2.6 h. Key challenges and future research directions are further discussed, including scalable manufacturing and the treatment of complex wastewater matrices. Full article
(This article belongs to the Special Issue Porous Materials for Wastewater Treatment (2nd Edition))
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