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The novel diiron amine complexes [Fe 2 Cp 2 (CO)(NH 2 R')(μ-CO){μ-CN(Me)(Cy)}]CF 3 SO 3 [R' = H, 3; Cy, 4; CH 2 CH 2 NH 2 , 5; CH 2 CH 2 NMe 2 , 6; CH 2 CH 2 (4-C 6 H 4 OMe), 7; CH 2 CH 2 (4-C 6 H 4 OH), 8; Cp = η 5 -C 5 H 5 , Cy = C 6 H 11  = cyclohexyl] were synthesized in 49-92 % yields from [Fe 2 Cp 2 (CO) 2 (μ-CO){μ-CN(Me)(Cy)}]CF 3 SO 3 , 1a, using a straightforward two-step procedure. They were characterized by IR and multinuclear NMR spectroscopy, and the structure of 7 was confirmed through X-ray diffraction analysis. Complexes 3-8 and the acetonitrile adducts [Fe 2 Cp 2 (CO)(NCMe)(μ-CO){μ-CN(Me)(R)}]CF 3 SO 3 (R = Cy, 2a; Me, 2b; Xyl = 2,6-C 6 H 3 Me 2 , 2c) were assessed for their water solubility, octanol-water partition coefficient and stability in physiological-like solutions. The in vitro antiproliferative activity of 2a-c and 3-8 was tested on seven human cancer cell lines (A2780, A2780R, PC3, A549, MCF7, HOS and HT-29), while the selectivity was evaluated using normal MRC-5 cells. Overall, the complexes exhibited variable cytotoxicity, with IC 50 values reaching the low micromolar range for 3, 7 and 8 in A2780 and A2780R cells, along with significant selectivity. Targeted experiments covered cell cycle modification, induction of cell death, mitochondrial membrane potential, ROS production and interaction with DNA and bovine serum albumin (BSA) as a model protein. The interaction of 3 with BSA was further investigated through computational studies. Results showed a negligible increase in intracellular ROS levels (except for 2b) and insignificant changes in mitochondrial membrane potential., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

The outbreak of antibiotic-resistant bacteria, or "superbugs", poses a global public health hazard due to their resilience against the most effective last-line antibiotics. Identifying potent antibacterial agents capable of evading bacterial resistance mechanisms represents the ultimate defense strategy. This study shows that -the otherwise essential micronutrient- manganese turns into a broad-spectrum potent antibiotic when coordinated with a carboxylated nitrogen-doped graphene. This antibiotic material (termed NGA-Mn) not only inhibits the growth of a wide spectrum of multidrug-resistant bacteria but also heals wounds infected by bacteria in vivo and, most importantly, effectively evades bacterial resistance development. NGA-Mn exhibits up to 25-fold higher cytocompatibility to human cells than its minimum bacterial inhibitory concentration, demonstrating its potential as a next-generation antibacterial agent. Experimental findings suggest that NGA-Mn acts on the outer side of the bacterial cell membrane via a multimolecular collective binding, blocking vital functions in both Gram-positive and Gram-negative bacteria. The results underscore the potential of single-atom engineering toward potent antibiotics, offering simultaneously a long-sought solution for evading drug resistance development while being cytocompatible to human cells., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Copper(ii) and zinc(ii) complexes with lapachol (HLap) of the composition [M(Lap) 2 (N-N)] and [Cu(Lap)(H 2 O)(terpy)]NO 3 (4), where M = Cu (1-3) or Zn (for 5-7), and N-N stands for bathophenanthroline (1 and 5), 5-methyl-1,10-phenanthroline (2 and 6), 2,2'-bipyridine (3), 2,2';6',2''-terpyridine (terpy, 4) and 1,10-phenanthroline (7), were synthesised and characterised. Complexes 1-5 revealed strong in vitro antiproliferative effects against A2780, A2780R, MCF-7, PC-3, A549 and HOS human cancer lines and MRC-5 normal cells, with IC 50 values above 0.5 μM, and reasonable selectivity index (SI), with SI > 3.8 for IC 50 (MRC-5)/IC 50 (A2780). Considerable time-dependent cytotoxicity in A2780 cells was observed for complexes 6 and 7, with IC 50 > 50 μM (24 h) to ca. 4 μM (48 h). Cellular effects of complexes 1, 5 and 7 in A2780 cells were investigated by flow cytometry revealing that the most cytotoxic complexes (1 and 5) significantly perturbed the mitochondrial membrane potential and the interaction with mitochondrial metabolism followed by the triggering of the intracellular pathway of apoptosis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Two copper(II) complexes containing diplacone (H 4 dipl), a naturally occurring C-geranylated flavanone derivative, in combination with bathophenanthroline (bphen) or 1,10-phenanthroline (phen) with the composition [Cu 3 (bphen) 3 (Hdipl) 2 ]⋅2H 2 O (1) and {[Cu(phen)(H 2 dipl) 2 ]⋅1.25H 2 O} n (2) were prepared and characterized. As compared to diplacone, the complexes enhanced in vitro cytotoxicity against A2780 and A2780R human ovarian cancer cells (IC 50  ≈ 0.4-1.2 μM), human lung carcinoma (A549, with IC 50  ≈ 2 μM) and osteosarcoma (HOS, with IC 50  ≈ 3 μM). Cellular effects of the complexes in A2780 cells were studied using flow cytometry, covering studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production. These results uncovered a possible mechanism of action characterized by the G2/M cell cycle arrest. The studies on human endothelial cells revealed that complexes 1 and 2, as well as their parental compound diplacone, do possess anti-inflammatory activity in terms of NF-κB inhibition. As for the effects on PPARα and/or PPARγ, complex 2 reduced the expression of leukocyte adhesion molecules VCAM-1 and E-selectin suggesting its dual anti-inflammatory capacity. A wide variety of Cu-containing coordination species and free diplacone ligand were proved by mass spectrometry studies in water-containing media, which might be responsible for multimodal effect of the complexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Structurally diverse zinc(II) complexes with tripodal tetradentate phenolic-amines of variable substituents in the phenol and amine moieties were synthesized and thoroughly characterized. The two dinuclear [Zn 2 (L 1 ) 2 ](ClO 4 ) 2 ·MeOH (1), [Zn 2 (L 2 ) 2 ](ClO 4 ) 2 (2), and four mononuclear [Zn(L 3 )(H 2 O)]·MeOH (3), [Zn(L 4 )] (4), [Zn(L 5 )] (5) and [Zn(L 6 )] (6) complexes revealed distorted octahedral, trigonal-bipyramidal or tetrahedral geometries. The free HL1 and H2L3-6 ligands, and complexes 1-6 were evaluated for in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3 and 22Rv1) and normal healthy MRC-5 cells. Overall results revealed high-to-moderate cytotoxicity (with the best IC 50 values for complex 6 ranging from 2.4 to 4.5 μM), which is however, significantly higher than that of the reference drug cisplatin. The moderately active complexes 1-4 showed considerable selectivity on A2780 cells (IC 50 ≈ 16.3-19.5 μM) over MRC-5 ones (with IC 50 >50 μM for 1, 2 and 4, and with IC 50 >25 μM for 3). The complexes 1, 2, and 6 and the ligand H2L6 were chosen for subsequent deeper biological evaluations. Their time-resolved cellular uptake and other cellular effects in A2780 cells were studied, such as cell cycle profile, intracellular ROS production, induction of apoptosis and activation of caspases 3/7. Complexes 1 and 2 caused significant G0/G1 cell cycle arrest in A2780 cells and antioxidant effects at normal conditions. They showed only limited effects on cellular processes connected with cytotoxicity, i.e. induction of apoptosis, depletion of mitochondrial membrane potential, and autophagy. These findings can be at least partly attributed to the low ability of the complexes to enter the A2780 cells and the depression of metabolic activity of the target cancer cells.

A bis(chalcone) molecule (H 2 L) was synthesized via Aldol's condensation from terephthalaldehyde and 2'-hydroxyacetophenone and it was used as bridging ligand for the preparation of five dinuclear copper(II) complexes of the composition [Cu(NN)(μ-L)Cu(NN)](NO 3 ) 2 ⋅nH 2 O (n = 0-2) (1-5), where NN stands for a bidentate N-donor ligand such as phen (1,10-phenanthroline, 1), bpy (2,2'-bipyridine, 2), mebpy (5,5'-dimethyl-2,2'-dipyridine, 3), bphen (bathophenanthroline, 4) and nphen (5-nitro-1,10-phenanthroline, 5). The compounds were characterized by different suitable techniques to confirm their purity, composition, and structure. Moreover, the products were evaluated for their in vitro cytotoxicity on a panel of human cancer cell lines: ovarian (A2780), ovarian resistant to cisplatin (A2780R), prostate (PC3), osteosarcoma (HOS), breast (MCF7) and lung (A549), and normal fibroblasts (MRC-5), showing significant cytotoxicity in most cases, with IC 50  ≈ 0.35-7.8 μM. Additionally, the time-dependent cytotoxicity and cellular uptake of copper, together with flow cytometric studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/superoxide production in A2780 cells, were also performed. The results of biological testing on A2780 cells pointed out a possible mechanism of action characterized by the G2/M cell cycle arrest and induction of apoptosis by triggering the intrinsic signalling pathway associated with the damage of mitochondrial structure and depletion of mitochondrial membrane potential. SYNOPSIS: Dinuclear Cu(II) complexes bearing a bridging bis(chalcone) ligand revealed high in vitro cytotoxicity, initiated A2780 cell arrest at G2/M phase and efficiently triggered intrinsic pathway of apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

GO is a 2D nanomaterial that has attracted attention in many industries in recent years, such as the chemical industry, electronics or medicine. Due to its unique properties such as strength, hydrophilicity and large specific surface area with the possibility of functionalization, GO is a particularly attractive material in biomedicine as a candidate for use in targeted drug delivery. In such a case, we need information on whether graphene oxide penetrates into cells and whether we are able to detect and monitor GO in these cells during and also after the treatment to evaluate possible degradation process of GO and its interaction within the cell compartements. This work introduces the Raman spectroscopy as label-free detection method showing the advantages of combining Raman spectroscopy with MCR (Multivariate Curve Resolution) analysis for advanced detection of GO in cervical cancer (HeLa) cells. Our synthesized GO is characterized firstly by AFM, SEM and Raman spectroscopy and then MCR-Raman spectroscopy is used to detect internalized GO in individual HeLa cells. Moreover, by using our methodology, distribution of GO as well as its chemical stability inside the cell for up to six months is investigated without using any additional labeling or tracing the GO. Thus, MCR-Raman spectroscopy may become a new analytical tool in preclinical and clinical applications of graphene-based nanotheranostics.

Motivated by the clinical success of gold(I) metallotherapeutic Auranofin in the effective treatment of both inflammatory and cancer diseases, we decided to prepare, characterize, and further study the [Au(kin)(PPh 3 )] complex ( 1 ), where Hkin = kinetin, 6-furfuryladenine, for its in vitro anti-cancer and anti-inflammatory activities. The results revealed that the complex ( 1 ) had significant in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, and THP-1), with IC 50 ≈ 1-5 μM, which was even significantly better than that for the conventional platinum-based drug Cisplatin while comparable with Auranofin . Although its ability to inhibit transcription factor NF-κB activity did not exceed the comparative drug Auranofin , it has been found that it is able to positively influence peroxisome-proliferator-activated receptor-gamma (PPARγ), and as a consequence of this to have the impact of moderating/reducing inflammation. The cellular effects of the complex ( 1 ) in A2780 cancer cells were also investigated by cell cycle analysis, induction of apoptosis, intracellular ROS production, activation of caspases 3/7 and disruption of mitochondrial membrane potential, and shotgun proteomic analysis. Proteomic analysis of R2780 cells treated with complex ( 1 ) and starting compounds revealed possible different places of the effect of the studied compounds. Moreover, the time-dependent cellular accumulation of copper was studied by means of the mass spectrometry study with the aim of exploring the possible mechanisms responsible for its biological effects.

Two cationic [Cu 2 (L 1-2 ) 2 ](ClO 4 ) 2 (1, 2), and four neutral doubly bridged-phenoxido-copper(II) complexes [Cu 2 (L 3-4 ) 2 ] (3, 4) and [Cu 2 (L 5-6 ) 2 (H 2 O)]‧2H 2 O (5, 6) as well as 1D polymeric catena-[Cu(L 7 )] (7), where HL 1-2 and H 2 L 3-7 represent tripodal tetradentate pyridyl or aliphatic-amino groups based 2,4-disubstituted phenolates, were synthesized and thoroughly characterized by various spectroscopic methods and single crystal X-ray analysis. The molecular structures of the complexes exhibited diverse geometrical environments around the central Cu(II) atoms. The in vitro antiproliferative activity of the isolated complexes and selected parent free ligands were screened against some human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, MCF-7). The most promising cytotoxicity against cancer cells were obtained for 1-6, while complex 6 was found as the best performing as compared to the reference drug cisplatin. The cytotoxicity study of complex 6 was therefore extended to wider variety of cancer cell lines (HOS, A549, PANC-1, CaCo2, HeLa) and results revealed its significant cytotoxicity on all investigated human cancer cells. The cell uptake study showed that cytotoxicity of 6 (3 μM concentration and 24 h of incubation) against A2780 cells was almost independent from the intracellular levels of copper. The effect of complexes 4, 6 and 7 on cell cycle of A2780 cells indicates that the mechanism of action in these complexes is not only different from that of cisplatin but also different among them. Complex 7 was able to induce apoptosis in A2780 cells, while complexes 4 and 6 did not and on the other hand, they showed considerable effect on autophagy induction and there are some clues that these complexes were able to induce cuproptosis in A2780 cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Recent experience with the COVID-19 pandemic should be a lesson learnt with respect to the effort we have to invest in the development of new strategies for the treatment of viral diseases, along with their cheap, easy, sensitive, and selective detection. Since we live in a globalized world where just hours can play a crucial role in the spread of a virus, its detection must be as quick as possible. Thanks to their chemical stability, photostability, and superior biocompatibility, carbon dots are a kind of nanomaterial showing great potential in both the detection of various virus strains and a broad-spectrum antiviral therapy. The biosensing and antiviral properties of carbon dots can be tuned by the selection of synthesis precursors as well as by easy post-synthetic functionalization. In this review, we will first summarize current options of virus detection utilizing carbon dots by either electrochemical or optical biosensing approaches. Secondly, we will cover and share the up-to-date knowledge of carbon dots' antiviral properties, which showed promising activity against various types of viruses including SARS-CoV-2. The mechanisms of their antiviral actions will be further adressed as well. Finally, we will discuss the advantages and distadvantages of the use of carbon dots in the tangled battle against viral infections in order to provide valuable informations for further research and development of new virus biosensors and antiviral therapeutics., (© 2021. The Author(s).)

Nanoparticle-sensitized photoporation is an upcoming approach for the intracellular delivery of biologics, combining high efficiency and throughput with excellent cell viability. However, as it relies on close contact between nanoparticles and cells, its translation towards clinical applications is hampered by safety and regulatory concerns. Here we show that light-sensitive iron oxide nanoparticles embedded in biocompatible electrospun nanofibres induce membrane permeabilization by photothermal effects without direct cellular contact with the nanoparticles. The photothermal nanofibres have been successfully used to deliver effector molecules, including CRISPR-Cas9 ribonucleoprotein complexes and short interfering RNA, to adherent and suspension cells, including embryonic stem cells and hard-to-transfect T cells, without affecting cell proliferation or phenotype. In vivo experiments furthermore demonstrated successful tumour regression in mice treated with chimeric antibody receptor T cells in which the expression of programmed cell death protein 1 (PD1) is downregulated after nanofibre photoporation with short interfering RNA to PD1. In conclusion, cell membrane permeabilization with photothermal nanofibres is a promising concept towards the safe and more efficient production of engineered cells for therapeutic applications, including stem cell or adoptive T cell therapy., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Different approaches for the determination of the 87 Sr/ 86 Sr isotope ratio of high-Rb glass are compared in this work to assess the suitability of minimally invasive approaches for applications on medieval stained glass (from the ancient Abbey of Stavelot in Belgium). It was found that pneumatic nebulization multicollector inductively coupled plasma-mass spectrometry (PN-MC-ICP-MS) after acid digestion and chromatographic isolation of the target analyte out of the sample matrix can still be seen as the preferred method for the high-precision isotopic analysis of Sr in glass with high Rb and rare-earth element (REE) concentrations. Alternatively, the use of laser ablation (LA) for sample introduction is a powerful technique for the direct analysis of solid samples. However, both the high Rb/Sr ratios in the samples of interest and the presence of REEs at sufficiently high concentrations lead to a large bias in LA-MC-ICP-MS, which cannot be corrected for, even by operating the MC-ICP-MS instrument at higher mass resolution and/or using mathematical corrections. It was demonstrated that LA tandem-ICP-MS (LA-ICP-MS/MS) using CH 3 F/He as the reaction gas to overcome spectral overlap in a mass-shift approach (chemical resolution) provides a viable alternative when (quasi) nondestructive analysis is required. This approach relies on the monitoring of Sr + ( m/z = 86, 87, and 88) ions as the corresponding SrF + reaction product ions ( m/z = 105, 106, and 107), thus avoiding the occurrence of spectral interference. Self-evidently, the isotope ratio precision attainable using sequential quadrupole-based ICP-MS instrumentation (0.3% RSD) was found to be significantly worse than that of high-precision MC-ICP-MS (0.03% RSD) with simultaneous detection, although it was still fit for the purpose of current applications. In addition to Sr isotopic analysis, the REE patterns and their potential influence on the Sr isotopic composition were evaluated by LA-ICP-MS., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Magnetic iron oxide nanocrystals (MIONs) are established as potent theranostic nanoplatforms due to their biocompatibility and the multifunctionality of their spin-active atomic framework. Recent insights have also unveiled their attractive near-infrared photothermal properties, which are, however, limited by their low near-infrared absorbance, resulting in noncompetitive photothermal conversion efficiencies (PCEs). Herein, we report on the dramatically improved photothermal conversion of condensed clustered MIONs, reaching an ultrahigh PCE of 71% at 808 nm, surpassing the so-far MION-based photothermal agents and even benchmark near-infrared photothermal nanomaterials. Moreover, their surface passivation is achieved through a simple self-assembly process, securing high colloidal stability and structural integrity in complex biological media. The bifunctional polymeric canopy simultaneously provided binding sites for anchoring additional cargo, such as a strong near-infrared-absorbing and fluorescent dye, enabling in vivo optical and photoacoustic imaging in deep tissues, while the iron oxide core ensures detection by magnetic resonance imaging. In vitro studies also highlighted a synergy-amplified photothermal effect that significantly reduces the viability of A549 cancer cells upon 808 nm laser irradiation. Integration of such-previously elusive-photophysical properties with simple and cost-effective nanoengineering through self-assembly represents a significant step toward sophisticated nanotheranostics, with great potential in the field of nanomedicine.

The ability of bacteria to develop resistance to antibiotics is threatening one of the pillars of modern medicine. It was recently understood that bacteria can develop resistance even to silver nanoparticles by starting to produce flagellin, a protein which induces their aggregation and deactivation. This study shows that silver covalently bound to cyanographene (GCN/Ag) kills silver-nanoparticle-resistant bacteria at concentrations 30 times lower than silver nanoparticles, a challenge which has been so far unmet. Tested also against multidrug resistant strains, the antibacterial activity of GCN/Ag is systematically found as potent as that of free ionic silver or 10 nm colloidal silver nanoparticles. Owing to the strong and multiple dative bonds between the nitrile groups of cyanographene and silver, as theory and experiments confirm, there is marginal silver ion leaching, even after six months of storage, and thus very high cytocompatibility to human cells. Molecular dynamics simulations suggest strong interaction of GCN/Ag with the bacterial membrane, and as corroborated by experiments, the antibacterial activity does not rely on the release of silver nanoparticles or ions. Endowed with these properties, GCN/Ag shows that rigid supports selectively and densely functionalized with potent silver-binding ligands, such as cyanographene, may open new avenues against microbial resistance., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

This study presents a toxicological evaluation of two types of carbon dots (CD), similar in size (<10 nm) but differing in surface charge. Whole-genome mRNA and miRNA expression (RNAseq), as well as gene-specific DNA methylation changes, were analyzed in human embryonic lung fibroblasts (HEL 12469) after 4 h and 24 h exposure to concentrations of 10 and 50 µg/mL (for positive charged CD; pCD) or 10 and 100 µg/mL (for negative charged CD, nCD). The results showed a distinct response for the tested nanomaterials (NMs). The exposure to pCD induced the expression of a substantially lower number of mRNAs than those to nCD, with few commonly differentially expressed genes between the two CDs. For both CDs, the number of deregulated mRNAs increased with the dose and exposure time. The pathway analysis revealed a deregulation of processes associated with immune response, tumorigenesis and cell cycle regulation, after exposure to pCD. For nCD treatment, pathways relating to cell proliferation, apoptosis, oxidative stress, gene expression, and cycle regulation were detected. The expression of miRNAs followed a similar pattern: more pronounced changes after nCD exposure and few commonly differentially expressed miRNAs between the two CDs. For both CDs the pathway analysis based on miRNA-mRNA interactions, showed a deregulation of cancer-related pathways, immune processes and processes involved in extracellular matrix interactions. DNA methylation was not affected by exposure to any of the two CDs. In summary, although the tested CDs induced distinct responses on the level of mRNA and miRNA expression, pathway analyses revealed a potential common biological impact of both NMs independent of their surface charge.

Although Ddi1-like proteins are conserved among eukaryotes, their biological functions remain poorly characterized. Yeast Ddi1 has been implicated in cell cycle regulation, DNA-damage response, and exocytosis. By virtue of its ubiquitin-like (UBL) and ubiquitin-associated (UBA) domains, it has been proposed to serve as a proteasomal shuttle factor. All Ddi1-like family members also contain a highly conserved retroviral protease-like (RVP) domain with unknown substrate specificity. While the structure and biological function of yeast Ddi1 have been investigated, no such analysis is available for the human homologs. To address this, we solved the 3D structures of the human Ddi2 UBL and RVP domains and identified a new helical domain that extends on either side of the RVP dimer. While Ddi1-like proteins from all vertebrates lack a UBA domain, we identify a novel ubiquitin-interacting motif (UIM) located at the C-terminus of the protein. The UIM showed a weak yet specific affinity towards ubiquitin, as did the Ddi2 UBL domain. However, the full-length Ddi2 protein is unable to bind to di-ubiquitin chains. While proteomic analysis revealed no activity, implying that the protease requires other factors for activation, our structural characterization of all domains of human Ddi2 sets the stage for further characterization.