N-Heterocyclic Carbenes as Ligands to Au(I)-Radiolabeled Compounds: A New Platform for Radiopharmaceutical Design.

The radionuclide Au, with a half-life of 2.7 days, emits γ radiation ideal for diagnostic purposes and generates β particles suitable for effective cancer radiotherapy, making it a perfect nuclide for "theranostics". However, the application of coordination compounds of Au(I)/Au(III) in medicine is limited by their instability in vivo.

GRPR-targeted gold nanoparticles as selective radiotherapy enhancers in glioblastoma.

Glioblastoma multiforme (GBM) is the most diagnosed primary brain tumor in adults and remains associated with a poor prognosis due to its aggressive nature. As tumor recurrence is often observed after standard radiation treatment, the use of gold nanoparticles (AuNPs) to improve radiotherapy effectiveness has been proposed as an advanced treatment strategy for this condition. Toward this goal, we investigated the radiosensitizing potential of gastrin releasing peptide receptor (GRPR)-targeted gold nanoparticles (AuNP-BBN) carrying a bombesin peptide (BBN) in glioblastoma cells, when combined withand x-ray radiation and in comparison with their non-targeted counterpart (AuNP-DOTA).

Harnessing the power of biosensors for environmental monitoring of pesticides in water.

The current strong reliance on synthetic chemicals, namely pesticides, is far from environmentally sustainable. These xenobiotics contribute significantly to global change and to the current biodiversity crisis, but have been overlooked when compared to other agents (e.g.

Mitochondria-tropic radioconjugates to enhance the therapeutic potential of terbium-161.

Background: Strategies that focus on delivering Auger electron emitters to highly radiosensitive intracellular targets-such as the nucleus, cell membrane, or mitochondria-are gaining attention. Targeting these organelles could enhance therapeutic efficacy while minimizing off-target toxicity by allowing lower administered doses. In this context, this study explores the therapeutic potential of Tb-labeled radiocomplexes that integrate the mitochondria-targeting triphenylphosphonium (TPP) moiety with a prostate-specific membrane antigen (PSMA) targeting vector.

Recommendations for reporting preclinical radiobiological studies in targeted radionuclide therapy.

The growing interest and investments in targeted radionuclide therapy (TRT) have expanded research efforts across preclinical and clinical domains. Researchers from diverse fields, including nuclear medicine, radiochemistry, radiopharmacy, radiotherapy, biology, and physics, are increasingly focusing on TRT. Despite this, a lack of standardization in preclinical radiobiological studies hinders the evaluation and comparison of therapeutic radiopharmaceuticals across laboratories.

Synthesis and Evaluation of Cytotoxic Activity of RuCp(II) Complexes Bearing (Iso)nicotinic Acid Based Ligands.

Background/objectives: Cancer remains one of the major challenges of our century. Organometallic ruthenium complexes are gaining recognition as a highly promising group of compounds in the development of cancer treatments.

Methods: Building on the auspicious results obtained for [Ru(η-CH)(PPh)(bipy)][CFSO] (TM34), our focus has shifted to examining the effects of incorporating bioactive ligands into the TM34 framework, particularly within the cyclopentadienyl ring.

Exploring wine yeast natural biodiversity to select strains with enological traits adapted to climate change.

Wine is widely consumed throughout the world and represents a significant financial market, but production faces increasing challenges. While consumers progressively value more complex flavor profiles, regional authenticity, and decreased use of additives, winemakers strive for consistency among climate change, characterized by rising environmental temperatures and sun burn events. This often leads to grapes reaching phenolic maturity with higher sugar levels, and increased microbial spoilage risk.

A versatile yeast model identifies the pesticides cymoxanil and metalaxyl as risk factors for synucleinopathies.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the presence of Lewy bodies, which predominantly consist of aggregated forms of the protein alpha-synuclein (aSyn). While these aggregates are a pathological hallmark of PD, the etiology of most cases remains elusive. Although environmental risk factors have been identified, such as the pesticides dieldrin and MTPT, many others remain to be assessed and their molecular impacts are underexplored.

Enhanced Cytotoxicity against a Pancreatic Cancer Cell Line Combining Radiation and Gold Nanoparticles.

The present work consisted of an exploratory study aiming to evaluate in vitro the potential of AuNPs during Radiation Therapy (RT) in human pancreatic adenocarcinoma cells. AuNPs coated with hyaluronic and oleic acids (HAOA-AuNPs) or with bombesin peptides (BBN-AuNPs) were used. AuNPs were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering.

The fungicide cymoxanil impairs respiration in Saccharomyces cerevisiae via cytochrome c oxidase inhibition.

Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae, we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and isolated mitochondria, specifically inhibiting cytochrome c oxidase (CcO) activity during oxidative phosphorylation.

Dual FGFR-targeting and pH-activatable ruthenium-peptide conjugates for targeted therapy of breast cancer.

Dysregulation of Fibroblast Growth Factor Receptors (FGFRs) signaling has been associated with breast cancer, yet employing FGFR-targeted delivery systems to improve the efficacy of cytotoxic agents is still sparsely exploited. Herein, we report four new bi-functional ruthenium-peptide conjugates (RuPCs) with FGFR-targeting and pH-dependent releasing abilities, envisioning the selective delivery of cytotoxic Ru complexes to FGFR(+)-breast cancer cells, and controlled activation at the acidic tumoral microenvironment. The antiproliferative potential of the RuPCs and free Ru complexes was evaluated in four breast cancer cell lines with different FGFR expression levels (SKBR-3, MDA-MB-134-VI, MCF-7, and MDA-MB-231) and in human dermal fibroblasts (HDF), at pH 6.

Evaluation of the theranostic potential of [Cu]CuCl in glioblastoma spheroids.

Background: Glioblastoma is an extremely aggressive malignant tumor with a very poor prognosis. Due to the increased proliferation rate of glioblastoma, there is the development of hypoxic regions, characterized by an increased concentration of copper (Cu). Considering this, Cu has attracted attention as a possible theranostic radionuclide for glioblastoma.

Utility of realistic microscopy-based cell models in simulation studies of nanoparticle-enhanced photon radiotherapy.

To enhance the effect of radiation on the tumor without increasing the dose to the patient, the combination of high-Z nanoparticles with radiotherapy has been proposed. In this work, we investigate the effects of the physical parameters of nanoparticles (NPs) on the Dose Enhancement Factor (DEF), and on the Sensitive Enhancement Ratio (SER) by applying a version of the Linear Quadratic Model. A method for constructing voxelized realistic cell geometries in Monte Carlo simulations from confocal microscopy images was developed and applied to Gliobastoma Multiforme cell lines (U87 and U373).

Novel yeast-based biosensor for environmental monitoring of tebuconazole.

Due to increasing demand for high and stable crop production, human populations are highly dependent on pesticide use for growing and storing food. Environmental monitoring of these agrochemicals is therefore of utmost importance, because of their collateral effects on ecosystem and human health. Even though most current-use analytical methods achieve low detection limits, they require procedures that are too complex and costly for routine monitoring.

Cancer 3D Models for Metallodrug Preclinical Testing.

Despite being standard tools in research, the application of cellular and animal models in drug development is hindered by several limitations, such as limited translational significance, animal ethics, and inter-species physiological differences. In this regard, 3D cellular models can be presented as a step forward in biomedical research, allowing for mimicking tissue complexity more accurately than traditional 2D models, while also contributing to reducing the use of animal models. In cancer research, 3D models have the potential to replicate the tumor microenvironment, which is a key modulator of cancer cell behavior and drug response.

Cu(II) and Zn(II) Complexes of New 8-Hydroxyquinoline Schiff Bases: Investigating Their Structure, Solution Speciation, and Anticancer Potential.

We report the synthesis and characterization of three novel Schiff bases (-) derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with amines containing morpholine or piperidine moieties. These were reacted with CuCl and ZnCl yielding six new coordination compounds, with the general formula ML, where M = Cu(II) or Zn(II) and L = -, which were all characterized by analytical, spectroscopic (Fourier transform infrared (FTIR), UV-visible absorption, nuclear magnetic resonance (NMR), or electron paramagnetic resonance (EPR)), and mass spectrometric techniques, as well as by single-crystal X-ray diffraction. In the solid state, two Cu(II) complexes, with and , are obtained as dinuclear compounds, with relatively short Cu-Cu distances (3.

Gallium and indium complexes with isoniazid-derived ligands: Interaction with biomolecules and biological activity against cancer cells and Mycobacterium tuberculosis.

Gallium and indium octahedral complexes with isoniazid derivative ligands were successfully prepared. The ligands, isonicotinoyl benzoylacetone (HL) and 4-chlorobenzoylacetone isonicotinoyl hydrazone (HL), and their respective coordination compounds with gallium and indium [GaL(HL)] (GaL), [GaL(HL)] (GaL), [InL(HL)] (InL) and [InL(HL)] (InL) were investigated by NMR, ESI-MS, UV-Vis, IR, single-crystal X-ray diffraction and elemental analysis. In vitro interaction studies with human serum albumin (HSA) evidenced a moderate affinity of all complexes with HSA through spontaneous hydrophobic interactions.

Boron clusters (ferrabisdicarbollides) shaping the future as radiosensitizers for multimodal (chemo/radio/PBFR) therapy of glioblastoma.

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, and is highly resistant to conventional radiotherapy and chemotherapy. Therefore, the development of multidrug resistance and tumor recurrence are frequent. Given the poor survival with the current treatments, new therapeutic strategies are urgently needed.

Radiation as a Tool against Neurodegeneration-A Potential Treatment for Amyloidosis in the Central Nervous System.

Radiotherapy (RT) is a relatively safe and established treatment for cancer, where the goal is to kill tumoral cells with the lowest toxicity to healthy tissues. Using it for disorders involving cell loss is counterintuitive. However, ionizing radiation has a hormetic nature: it can have deleterious or beneficial effects depending on how it is applied.

Searching for a Paradigm Shift in Auger-Electron Cancer Therapy with Tumor-Specific Radiopeptides Targeting the Mitochondria and/or the Cell Nucleus.

Although Tc is not an ideal Auger electron (AE) emitter for Targeted Radionuclide Therapy (TRT) due to its relatively low Auger electron yield, it can be considered a readily available "model" radionuclide useful to validate the design of new classes of AE-emitting radioconjugates. With this in mind, we performed a detailed study of the radiobiological effects and mechanisms of cell death induced by the dual-targeted radioconjugates and (TPP = triphenylphosphonium; AO = acridine orange; BBN = bombesin derivative) in human prostate cancer PC3 cells. and caused a remarkably high reduction of the survival of PC3 cells when compared with the single-targeted congener , leading to an augmented formation of γH2AX foci and micronuclei.

New iron(III) anti-cancer aminobisphenolate/phenanthroline complexes: Enhancing their therapeutic potential using nanoliposomes.

Malignant melanoma is an aggressive and deadly form of skin cancer and novel and improved therapeutic options are needed. A promising strategy involves the use of metallodrugs combined with liposomes for targeted delivery to cancer cells. In this work, a family of iron(III) complexes was synthesized bearing a trianionic aminobisphenolate ligand (L) and phenanthroline-type co-ligands (NN).

Cobaltabis(dicarbollide) ([-COSAN]) as Multifunctional Chemotherapeutics: A Prospective Application in Boron Neutron Capture Therapy (BNCT) for Glioblastoma.

Purpose: The aim of our study was to assess if the sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative (Na[-COSAN] and Na[8,8'-I--COSAN]) could be promising agents for dual anti-cancer treatment (chemotherapy + BNCT) for GBM.

Methods: The biological activities of the small molecules were evaluated in vitro with glioblastoma cells lines U87 and T98G in 2D and 3D cell models and in vivo in the small model animal () at the L4-stage and using the eggs.

Results: Our studies indicated that only spheroids from the U87 cell line have impaired growth after treatment with both compounds, suggesting an increased resistance from T98G spheroids, contrary to what was observed in the monolayer culture, which highlights the need to employ 3D models for future GBM studies.

Bioconjugate Supramolecular Pd Metallacages Penetrate the Blood Brain Barrier and .

The biomedical application of discrete supramolecular metal-based structures, specifically self-assembled metallacages, is still an emergent field of study. Capitalizing on the knowledge gained in recent years on the development of 3-dimensional (3D) metallacages as novel drug delivery systems and agents, we explore here the possibility to target [PdL] cages (L = 3,5-bis(3-ethynylpyridine)phenyl ligand) to the brain. In detail, a new water-soluble homoleptic cage () tethered to a blood brain barrier (BBB)-translocating peptide was synthesized by a combination of solid-phase peptide synthesis (SPPS) and self-assembly procedures.