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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(η5-C5H5)(PPh3)(bipy)][CF3SO3] (TM34), our focus has shifted to examining the effects of incorporating bioactive ligands into the TM34 framework, particularly within the cyclopentadienyl ring. Results: In this study, we report the synthesis and characterization of two new ruthenium(II) complexes with the general formula [Ru(η5-C5H4CCH3=R)(PPh3)(bipy)][CF3SO3], where R represents a nicotinic acid derivative (NNHCO(py-3-yl)) (1) or an isoniazid derivative (NNHCO(py-4-yl)) (2). The complexes were fully characterized using a combination of spectroscopic techniques and computational analysis, revealing the presence of E/Z-hydrazone isomerism. Stability studies confirmed the robustness of both complexes in biological media, with compound 1 maintaining good stability in buffer solutions mimicking physiological (pH 7.4) and tumor-like (pH 6.8) environments. The cytotoxicity of the complexes was evaluated in vitro in several human cancer cell lines, namely melanoma (A375), alveolar adenocarcinoma (A549), epidermoid carcinoma (A431), and breast cancer (MDA-MB 231). Conclusions: Both compounds exhibited moderate to high cytotoxic activity, with complex 1 showing a greater propensity to induce cell death, particularly in the A431 and MDA-MB 231 cell lines.

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. These features make cancer 3D models prime tools for the preclinical study of anti-tumoral drugs, especially considering that there is still a need to develop effective anti-cancer drugs with high selectivity, minimal toxicity, and reduced side effects. Metallodrugs, especially transition-metal-based complexes, have been extensively studied for their therapeutic potential in cancer therapy due to their distinctive properties; however, despite the benefits of 3D models, their application in metallodrug testing is currently limited. Thus, this article reviews some of the most common types of 3D models in cancer research, as well as the application of 3D models in metallodrug preclinical studies.

Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer‐related mortality, with poor survival due to late diagnosis and ineffective therapies. Aquaporin‐3 (AQP3) and AQP5 are transmembrane proteins overexpressed in PDAC, promoting tumor progression and metastasis, representing promising therapeutic targets. Here, we investigated their involvement in PDAC spheroids' growth and morphology using two human PDAC cell lines, BxPC‐3 and MiaPaca‐2. Treatment with AQP3 inhibitors decreased spheroids' diameter, area, and viability and altered MiaPaca‐2 spheroids' circularity, suggesting reduced growth. Similarly, silencing AQP3 or AQP5 in BxPC‐3 spheroids decreased spheroids' size with a more pronounced viability reduction, indicating impaired growth and cell death. This study demonstrates, for the first time, the critical roles of AQP3 and AQP5 in PDAC spheroids' development.

Background: Radiosensitizers can be used to enhance tumor response and mitigate toxicity in healthy tissues during radiation therapy. This study investigates the radiosensitizing potential of the metallacarborane Fe/57Fe-ferrabisdicarbollide in SK-BR-3 and MDA-MB-231 breast cancer cells, using two distinct gamma-photon sources: high-dose 60Co (2.08 Gy) and low-dose 57Co (37.55 mGy, 57Fe Mössbauer effect). Methods: We evaluated cell viability and survival in 2D monolayer and 3D spheroid cultures, as well as the mechanism of cell death (ROS production, apoptosis or necrosis). Computational dosimetry was used to calculate the average absorbed dose. Results: In 2D models, both radiation sources induced reduced viability and increased ROS, with distinct cell death patterns dependent on the source (apoptosis or necrosis). Comparing 2D and 3D MDA-MB-231 models revealed that spheroid survival was significantly more impaired. The low-dose 57Co source caused a significant radiosensitization in MDA-MB-231 spheroids, dramatically impacting viability and survival. This effect is attributed to the Mössbauer effect, where the resonant absorption of 14.41 keV radiation by 57Fe leads to a massive, localized dose enhancement. The subsequent cascade of Auger and conversion electrons (local high LET) caused significantly greater cellular damage than sparse photon radiation. Conclusions: Fe/57Fe-ferrabisdicarbollide demonstrates a potent radiosensitizing effect depending on the cell model and the radiation source used. Crucially, the observed radiosensitization allows for the development of a new, more efficient cancer radiotherapy approach that can achieve therapeutic efficacy using a significantly lower radiation dose to the patient. This paves the way for safer and better-tolerated cancer treatments.

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[sup.5] -C[sub.5] H[sub.5] )(PPh[sub.3] )(bipy)][CF[sub.3] SO[sub.3] ] (TM34), our focus has shifted to examining the effects of incorporating bioactive ligands into the TM34 framework, particularly within the cyclopentadienyl ring. Results: In this study, we report the synthesis and characterization of two new ruthenium(II) complexes with the general formula [Ru(η[sup.5] -C[sub.5] H[sub.4] CCH[sub.3] =R)(PPh[sub.3] )(bipy)][CF[sub.3] SO[sub.3] ], where R represents a nicotinic acid derivative (NNHCO(py-3-yl)) (1) or an isoniazid derivative (NNHCO(py-4-yl)) (2). The complexes were fully characterized using a combination of spectroscopic techniques and computational analysis, revealing the presence of E/Z -hydrazone isomerism. Stability studies confirmed the robustness of both complexes in biological media, with compound 1 maintaining good stability in buffer solutions mimicking physiological (pH 7.4) and tumor-like (pH 6.8) environments. The cytotoxicity of the complexes was evaluated in vitro in several human cancer cell lines, namely melanoma (A375), alveolar adenocarcinoma (A549), epidermoid carcinoma (A431), and breast cancer (MDA-MB 231). Conclusions: Both compounds exhibited moderate to high cytotoxic activity, with complex 1 showing a greater propensity to induce cell death, particularly in the A431 and MDA-MB 231 cell lines.

Radiosensitizers can be used to enhance tumor response and mitigate toxicity in healthy tissues during radiation therapy. This study investigates the radiosensitizing potential of the metallacarborane Fe/ Fe-ferrabisdicarbollide in SK-BR-3 and MDA-MB-231 breast cancer cells, using two distinct gamma-photon sources: high-dose Co (2.08 Gy) and low-dose Co (37.55 mGy, Fe Mössbauer effect). We evaluated cell viability and survival in 2D monolayer and 3D spheroid cultures, as well as the mechanism of cell death (ROS production, apoptosis or necrosis). Computational dosimetry was used to calculate the average absorbed dose. In 2D models, both radiation sources induced reduced viability and increased ROS, with distinct cell death patterns dependent on the source (apoptosis or necrosis). Comparing 2D and 3D MDA-MB-231 models revealed that spheroid survival was significantly more impaired. The low-dose Co source caused a significant radiosensitization in MDA-MB-231 spheroids, dramatically impacting viability and survival. This effect is attributed to the Mössbauer effect, where the resonant absorption of 14.41 keV radiation by Fe leads to a massive, localized dose enhancement. The subsequent cascade of Auger and conversion electrons (local high LET) caused significantly greater cellular damage than sparse photon radiation. Fe/ Fe-ferrabisdicarbollide demonstrates a potent radiosensitizing effect depending on the cell model and the radiation source used. Crucially, the observed radiosensitization allows for the development of a new, more efficient cancer radiotherapy approach that can achieve therapeutic efficacy using a significantly lower radiation dose to the patient. This paves the way for safer and better-tolerated cancer treatments.

Background: Radiosensitizers can be used to enhance tumor response and mitigate toxicity in healthy tissues during radiation therapy. This study investigates the radiosensitizing potential of the metallacarborane Fe/[sup.57]Fe-ferrabisdicarbollide in SK-BR-3 and MDA-MB-231 breast cancer cells, using two distinct gamma-photon sources: high-dose [sup.60]Co (2.08 Gy) and low-dose [sup.57]Co (37.55 mGy, [sup.57]Fe Mössbauer effect). Methods: We evaluated cell viability and survival in 2D monolayer and 3D spheroid cultures, as well as the mechanism of cell death (ROS production, apoptosis or necrosis). Computational dosimetry was used to calculate the average absorbed dose. Results: In 2D models, both radiation sources induced reduced viability and increased ROS, with distinct cell death patterns dependent on the source (apoptosis or necrosis). Comparing 2D and 3D MDA-MB-231 models revealed that spheroid survival was significantly more impaired. The low-dose [sup.57]Co source caused a significant radiosensitization in MDA-MB-231 spheroids, dramatically impacting viability and survival. This effect is attributed to the Mössbauer effect, where the resonant absorption of 14.41 keV radiation by [sup.57]Fe leads to a massive, localized dose enhancement. The subsequent cascade of Auger and conversion electrons (local high LET) caused significantly greater cellular damage than sparse photon radiation. Conclusions: Fe/[sup.57]Fe-ferrabisdicarbollide demonstrates a potent radiosensitizing effect depending on the cell model and the radiation source used. Crucially, the observed radiosensitization allows for the development of a new, more efficient cancer radiotherapy approach that can achieve therapeutic efficacy using a significantly lower radiation dose to the patient. This paves the way for safer and better-tolerated cancer treatments.

Fluctuations in the clonal composition of Group A Streptococcus (GAS) have been associated with the emergence of successful lineages and with upsurges of invasive infections (iGAS). This study aimed at identifying changes in the clones causing iGAS in Portugal. Antimicrobial susceptibility testing, emm typing and superantigen (SAg) gene profiling were performed for 381 iGAS isolates from 2010–2015. Macrolide resistance decreased to 4%, accompanied by the disappearance of the M phenotype and an increase of the iMLS B phenotype. The dominant emm types were: emm 1 (28%), emm 89 (11%), emm 3 (9%), emm 12 (8%), and emm 6 (7%). There were no significant changes in the prevalence of individual emm types, emm clusters, or SAg profiles when comparing to 2006–2009, although an overall increasing trend was recorded during 2000–2015 for emm 1, emm 75, and emm 87. Short-term increases in the prevalence of emm 3, emm 6, and emm 75 may have been driven by concomitant SAg profile changes observed within these emm types, or reflect the emergence of novel genomic variants of the same emm types carrying different SAgs.