Comparing organic and metallo-organic hydrazone molecular cages as potential carriers for doxorubicin delivery.

Molecular cages are three-dimensional supramolecular structures that completely wrap guest molecules by encapsulation. We describe a rare comparative study between a metallo-organic cage and a fully organic analogous system, obtained by hydrazone bond formation self-assembly. Both cages are able to encapsulate the anticancer drug doxorubicin, with the organic cage forming a 1 : 1 inclusion complex with μM affinity, whereas the metallo-organic host experiences disassembly by interaction with the drug.

β-Galactosidase-Triggered Photodynamic Elimination of Senescent Cells with a Boron Dipyrromethene-Based Photosensitizer.

Senescence is a cellular response having physiological and reparative functions to preserve tissue homeostasis and suppress tumor growth. However, the accumulation of senescent cells would cause deleterious effects that lead to age-related dysfunctions and cancer progression. Hence, selective detection and elimination of senescent cells are crucial yet remain a challenge.

Chemical Strategies for the Detection and Elimination of Senescent Cells.

Cellular senescence can be defined as an irreversible stopping of cell proliferation that arises in response to various stress signals. Cellular senescence is involved in diverse physiological and pathological processes in different tissues, exerting effects on processes as differentiated as embryogenesis, tissue repair and remodeling, cancer, aging, and tissue fibrosis. In addition, the development of some pathologies, aging, cancer, and other age-related diseases has been related to senescent cell accumulation.

A renal clearable fluorogenic probe for in vivo β-galactosidase activity detection during aging and senolysis.

Accumulation of senescent cells with age leads to tissue dysfunction and related diseases. Their detection in vivo still constitutes a challenge in aging research. We describe the generation of a fluorogenic probe (sulfonic-Cy7Gal) based on a galactose derivative, to serve as substrate for β-galactosidase, conjugated to a Cy7 fluorophore modified with sulfonic groups to enhance its ability to diffuse.

A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells.

Cellular senescence is implicated in the occurrence and progression of multiple age-related disorders. In this context, the selective elimination of senescent cells, senolysis, has emerged as an effective therapeutic strategy. However, the heterogeneous senescent phenotype hinders the discovery of a universal and robust senescence biomarker that limits the effective of senolytic with off-target toxic effects.

Detection and Elimination of Senescent Cells with a Self-Assembled Senescence-Associated β-Galactosidase-Activatable Nanophotosensitizer.

Senescent cells have become an important therapeutic target for many age-related dysfunctions and diseases. We report herein a novel nanophotosensitizing system that is responsive to the senescence-associated β-galactosidase (β-gal) for selective detection and elimination of these cells. It involves a dimeric zinc(II) phthalocyanine linked to a β-galactose unit via a self-immolative linker.

Time-Tested Strategies in Modern Context: A Bibliometric Study of Chemotherapy's Continued Importance in Colorectal Cancer Treatment.

In the landscape of colorectal cancer treatment, classical chemotherapeutic agents such as 5-fluorouracil, capecitabine, irinotecan, oxaliplatin, trifluridine, and tipiracil have historically played a pivotal role. This study presents a comprehensive bibliometric analysis of the top 100 most influential articles focusing on these classic chemotherapy drugs in the management of colorectal cancer. With this, we shed light on their current importance, despite the emergence of new therapeutic targets and treatments in the field of oncology.

Biosafety of mesoporous silica nanoparticles; towards clinical translation.

Mesoporous silica nanoparticles (MSNs) have attracted the attention of chemists, who have developed numerous systems for the encapsulation of a plethora of molecules, allowing the use of mesoporous silica nanoparticles for biomedical applications. MSNs have been extensively studied for their use in nanomedicine, in applications such as drug delivery, diagnosis, and bioimaging, demonstrating significant in vivo efficacy in different preclinical models. Nevertheless, for the transition of MSNs into clinical trials, it is imperative to understand the characteristics that make MSNs effective and safe.

Targeted Delivery of the Pan-Inflammasome Inhibitor MM01 as an Alternative Approach to Acute Lung Injury Therapy.

Acute lung injury (ALI) is a severe pulmonary disorder responsible for high percentage of mortality and morbidity in intensive care unit patients. Current treatments are ineffective, so the development of efficient and specific therapies is an unmet medical need. The activation of NLPR3 inflammasome during ALI produces the release of proinflammatory factors and pyroptosis, a proinflammatory form of cell death that contributes to lung damage spreading.

β-Galactosidase-Activatable Nile Blue-Based NIR Senoprobe for the Real-Time Detection of Cellular Senescence.

Cellular senescence is a stable cell cycle arrest in response to stress or other damage stimuli to maintain tissue homeostasis. However, the accumulation of senescent cells can lead to the progression of various senescence-related disorders. In this paper, we describe the development of a β-galactosidase-activatable near-infrared (NIR) senoprobe, , for the detection of senescent cells based on the use of the FDA-approved Nile blue () fluorophore.

Combination of palbociclib with navitoclax based-therapies enhances in vivo antitumoral activity in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a very aggressive subtype of breast cancer with a poor prognosis and limited effective therapeutic options. Induction of senescence, arrest of cell proliferation, has been explored as an effective method to limit tumor progression in metastatic breast cancer. However, relapses occur in some patients, possibly as a result of the accumulation of senescent tumor cells in the body after treatment, which promote metastasis.

Harmonization of indirect reference intervals calculation by the Bhattacharya method.

Objectives: The aim of this study was to harmonize the criteria for the Bhattacharya indirect method Microsoft Excel Spreadsheet for reference intervals calculation to reduce between-user variability and use these criteria to calculate and evaluate reference intervals for eight analytes in two different years.

Methods: Anonymized laboratory test results from outpatients were extracted from January 1st 2018 to December 31st 2019. To assure data quality, we examined the monthly results from an external quality control program.

Enhancement of photoactivity and cellular uptake of (BuN)[MoI(CHCOO)] complex by loading on porous MCM-41 support. Photodynamic studies as an anticancer agent.

The incorporation by ionic assembly of the hexanuclear molybdenum cluster (BuN)[MoI(CHCO)] (1) in amino-decorated mesoporous silica nanoparticles MCM-41, has yielded the new molybdenum-based hybrid photosensitizer 1@MCM-41. The new photoactive material presents a high porosity, due to the intrinsic high specific surface area of MCM-41 nanoparticles (989 m g) which is responsible for the good dispersion of the hexamolybdenum clusters on the nanoparticles surface, as observed by STEM analysis. The hybrid photosensitizer can generate efficiently singlet oxygen, which was demonstrated by using the benchmark photooxygenation reaction of 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABDA) in water.

Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy.

In this article, we report one of the few examples of nanoparticles capable of simultaneously delivering CRISPR-Cas9 gene-editing machinery and releasing drugs for one-shot treatments. Considering the complexity of inflammation in diseases, the synergistic effect of nanoparticles for gene-editing/drug therapy is evaluated in an in vitro inflammatory model as proof of concept. Mesoporous silica nanoparticles (MSNs), able to deliver the CRISPR/Cas9 machinery to edit gasdermin D (GSDMD), a key protein involved in inflammatory cell death, and the anti-inflammatory drug VX-765 (CRISPR-VX-MSNs), were prepared.

Performance evaluation of a point of care cartridge of the new GEM Premier ChemSTAT analyzer.

Background And Aims: GEM Premier ChemSTAT is a new point-of-care system providing rapid creatinine, BUN and tCO measurements together with electrolytes, metabolites, hematocrit, pH and pCO from a single whole blood specimen in acute care settings such as emergency departments and intensive care units. Accurate measurements of whole blood creatinine can aid in the diagnosis and treatment of renal diseases.

Materials And Methods: Heparinized whole blood samples from different clinical locations were evaluated on the GEM Premier ChemSTAT and results compared to plasma from the same samples on the Beckman AU5800 or whole blood on the GEM Premier 4000.

Mesoporous Silica Materials as an Emerging Tool for Cancer Immunotherapy.

Cancer immunotherapy has emerged in the past decade as a promising strategy for treating many forms of cancer by stimulating the patient's immune system. Although immunotherapy has achieved some promising results in clinics, more efforts are required to improve the limitations of current treatments related to lack of effective and targeted cancer antigens delivery to immune cells, dose-limiting toxicity, and immune-mediated adverse effects, among others. In recent years, the use of nanomaterials has proven promising to enhance cancer immunotherapy efficacy and reduce side effects.

Pharmacological senolysis reduces doxorubicin-induced cardiotoxicity and improves cardiac function in mice.

Many anticancer agents used in clinics induce premature senescence in healthy tissues generating accelerated aging processes and adverse side-effects in patients. Cardiotoxicity is a well-known limiting factor of anticancer treatment with doxorubicin (DOX), a very effective anthracycline widely used as antitumoral therapy in clinical practice, that leads to long-term morbidity and mortality. DOX exposure severely affects the population of cardiac cells in both mice and human hearts by inducing premature senescence, which may represent the molecular basis of DOX-induced cardiomyopathy.

Development of Geometry-Controlled All-Orthogonal BODIPY Trimers for Photodynamic Therapy and Phototheragnosis.

We have established an easy synthetic protocol for selectively developing all-orthogonal BODIPY trimers with unprecedented geometries on the basis of selecting methyl oxidation versus electrophilic formylation of key dimeric precursors. Photophysical characterization together with biological assays unraveled the most suitable BODIPY-BODIPY geometrical arrangements within the trimer, forcing them to serve as molecular platforms for the development of new, advanced heavy-atom-free photosensitizers for photodynamic therapy and phototheragnosis.

Lipofuscin labeling through biorthogonal strain-promoted azide-alkyne cycloaddition for the detection of senescent cells.

A new method for senescent cell detection is described, which is based on lipofuscin labeling with a fluorescent reporter through a biorthogonal strain-promoted azide-alkyne cycloaddition. The sensing protocol involves a first step where the interaction of lipofuscin with a Sudan Black B derivative containing an azide moiety (SBB-N ) is carried out. In the final step, the azide moiety reacts with a fluorophore containing a cyclooctene ring (BODIPY).

Horseradish Peroxidase-Functionalized Gold Nanoconjugates for Breast Cancer Treatment Based on Enzyme Prodrug Therapy.

Introduction: Breast cancer has the highest mortality rate among cancers in women. Patients suffering from certain breast cancers, such as triple-negative breast cancer (TNBC), lack effective treatments. This represents a clinical concern due to the associated poor prognosis and high mortality.

Mesoporous silica nanoparticles for pulmonary drug delivery.

Over the last years, respiratory diseases represent a clinical concern, being included among the leading causes of death in the world due to the lack of effective lung therapies, mainly ascribed to the pulmonary barriers affecting the delivery of drugs to the lungs. In this way, nanomedicine has arisen as a promising approach to overcome the limitations of current therapies for pulmonary diseases. The use of nanoparticles allows enhancing drug bioavailability at the target site while minimizing undesired side effects.

Targeted-lung delivery of dexamethasone using gated mesoporous silica nanoparticles. A new therapeutic approach for acute lung injury treatment.

Acute lung injury (ALI) is a critical inflammatory syndrome, characterized by increased diffuse inflammation and severe lung damage, which represents a clinical concern due to the high morbidity and mortality in critical patients. In last years, there has been a need to develop more effective treatments for ALI, and targeted drug delivery to inflamed lungs has become an attractive research field. Here, we present a nanodevice based on mesoporous silica nanoparticles loaded with dexamethasone (a glucocorticoid extensively used for ALI treatment) and capped with a peptide that targets the TNFR1 receptor expressed in pro-inflammatory macrophages (TNFR-Dex-MSNs) and avoids cargo leakage.

A descriptive and validation study of a predictive model of severity of SARS-COV-2 infection.

Objectives: The strain the SARS-COV-2 pandemic is putting on hospitals requires that predictive values are identified for a rapid triage and management of patients at a higher risk of developing severe COVID-19. We developed and validated a prognostic model of COVID-19 severity.

Methods: A descriptive, comparative study of patients with positive vs.