Harnessing senolytics and PARP inhibition to expand the antitumor activity of CDK4/6 inhibitors in prostate cancer.

Metastatic prostate cancer (mPC) is a lethal disease; most therapeutic options focus on androgen receptor (AR) signalling inhibition, but resistance eventually arises. Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have shown antitumor efficacy in mPC preclinical models, but their efficacy in mPC clinical trials has been limited. We hypothesize that novel combination therapies designed leveraging mPC adaptation to CDK4/6i could lead to increased and sustained antitumor effect.

Targeting the senescent surfaceome through DPP4 antibody-functionalized nanoparticles. An application to cancer therapy.

Due to the heterogeneity of the senescent phenotype and the lack of a universal biomarker of senescence, the targeting of senescent cells is still an unresolved challenge, and the elimination of senescent cells using specific drugs (senolytics) is still limited in clinical use due to the off-target effects and associated toxicities of current therapeutic strategies. In this study, the induction of senescence in human melanoma cells by palbociclib is found to lead to a senescent phenotype characterized by overexpression of the membrane protein dipeptidyl peptidase 4 (DPP4), previously identified only in ageing contexts. Based on this discovery, a nanoparticle targeting DPP4 overexpression in the senescent surfaceome is designed, synthesized, and characterized to target senescent cancer cells.

Glucose-Fueled Gated Nanomotors: Enhancing Anticancer Efficacy via Deep Drug Penetration into Tumors.

Bioinspired nano/micromotors with drug delivery capabilities are emerging tools with the promising potential to treat numerous diseases. However, some major challenges must be overcome before reaching real biomedical applications. Above all, it is necessary to design engines that employ biocompatible and bioavailable fuels to induce efficient propulsion in biological environments.

Gated Nanosensor for Sulphate-Reducing Bacteria Detection.

is an anaerobic microorganism belonging to the group of sulphate-reducing bacteria (SRB). SRB form biofilms on metal surfaces in water supply networks, producing a microbiologically influenced corrosion (MIC). This process produces the deterioration of metal surfaces, leading to high economic costs and different environmental safety and health problems related to its chemical treatment.

Bacteriophage-Gated Optical Sensor for Bacteria Detection.

Bacterial infections significantly impact public health, and the growing threat of antimicrobial resistance underscores the urgent need for rapid and accessible diagnostic tools. This study presents a novel bacteriophage-gated sensor for the selective detection of . The sensor utilizes sulforhodamine B as a fluorescent reporter dye encapsulated in mesoporous silica particles, with bacteriophages acting as gatekeepers.

Natural antimicrobials synergistically coupled with nanomotors: An innovative strategy for biofilm eradication.

Biofilms are one of the most important problems occurring in industrial environments, especially in food industry. The possibility of foodborne disease outbreaks as a result of biofilm-food cross-contamination is a distinct concern, along with the substantial costs associated with food spoilage and biofilm control. Besides, despite daily cleaning and disinfection, many bacteria grow in machines and surfaces in food processing plants, some of them forming biofilms.

Assessment of the Toxicity of Free and PLGA-Encapsulated Phospholipase A2 CB: An In Vitro Approach.

Background: The use of bioactive molecules isolated from rattlesnake venom and other poisons has been ongoing for years. Among these bioactive compounds present in snake venom, crotoxin (CTX) stands out as a β-heterodimeric neurotoxin isolated from the venom of Crotalus durissus terrificus. Research on this toxin for its applicability to tumor inhibition has advanced to clinical trials in recent years.

Metabolomic Biomarkers of Pulmonary Fibrosis in COVID-19 Patients One Year After Hospital Discharge.

Coronavirus disease 2019 (COVID-19) global pandemic has affected more than 600 million people up to date. The symptomatology and severity of COVID-19 are very broad, and there are still concerns about the long-term sequelae that it can have on discharged patients. The development of pulmonary fibrotic sequelae after this infection is especially worrying.

Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery.

Hypoxia, i.e., low oxygen concentration at the tissue level, is a common feature of most solid tumors, and is responsible for their enhanced aggressiveness and resistance to chemotherapy, radiotherapy and photodynamic therapy.

Chemical characterization and encapsulation of extract with cytotoxic properties.

Mushrooms of the genus are known for diverse biological activities, demonstrated both traditionally and experimentally. Their secondary metabolites have shown cytotoxic potential across different cancer cell lines. Besides exploration of the most active components in different species or genotypes, new formulation techniques are in development.

Nanodevice-Mediated Immune Cell Recruitment: Targeting Senescent Cells via MMP-3-Responsive CXCL12-Coated Nanoparticles.

Senescent cells are involved in age-related disorders in different organs and are therapeutic targets for fibrotic and chronic pathologies. Immune-modulating agents, able to enhance senescent cell detection and elimination by endogenous immune cells, have emerged as pharmacological strategies. We report herein a nanoparticle for immune cell-mediated senolytic therapy designed to recruit immune cells in response to specific enzymatic matrix metalloproteinase-3 (MMP-3) activity in the senescence-associated secretory phenotype.

Renal-clearable probes for disease detection and monitoring.

The demand for novel, minimally invasive, cost-effective, and easily readable diagnostic tools, primarily designed for the longitudinal monitoring of diseases and their treatments, has promoted the development of diagnostic systems that selectively target cells, tissues, or organs, at the same time minimizing their nonspecific accumulation, thus reducing the risk of toxicity and side effects. In this review, we explore the development of renal-clearable systems in non-invasive or minimally invasive detection protocols, all with the objective of minimizing nonspecific accumulation and its associated toxicity effects through quick renal excretion. These probes can identify molecules of interest or different healthy states of the patients through the direct analysis of urine (urinalysis).

Antimicrobial Surfaces: Stainless Steel Functionalized with the Essential Oil Component Vanillin.

Pathogenic microorganisms can adhere to solid surfaces, leading to the formation of biofilms, thus building a physical barrier hindering the penetration and diffusion of antimicrobial compounds. In this context, the use of natural antimicrobial compounds, such as essential oil components, as substitutes for common synthetic antimicrobials in the fight to prevent antimicrobial resistance is explored. As stainless steel is one of the most widely used surfaces in different industries, we have developed an innovative antimicrobial treatment for stainless steel surfaces based on a multi-step functionalization process, in which the stainless steel surface is coated with a silica layer to which a vanillin derivative is covalently attached.

Synthesis of a PdL Hydrazone Molecular Cage Through Multiple Reaction Pathways.

Molecular cages are preorganized molecules with a central cavity, typically formed through the reaction of their building blocks through chemical bonds. This requires, in most cases, forming and breaking reversible bonds during the cage formation reaction pathway for error correction to drive the reaction to the cage product. In this work, we focus on both Pd-ligand and hydrazone bonds implemented in the structure of a PdL hydrazone molecular cage.

Copper-cobalt peroxide nanoparticles: a biomimetic cascade reaction for enhanced Fenton-like therapy at physiologically relevant pH.

Traditional Fenton-like reactions, commonly employed in chemodynamic therapy (CDT) for cancer treatment, face limitations due to the mildly acidic tumor microenvironment (TME) and scarce HO availability. Aiming to overcome these hurdles, we report herein the preparation of copper-cobalt peroxide (CCp) nanoparticles, a novel catalyst that enables a pH-activated, self-supplying HO-mediated cascade reaction. In the slightly acidic TME (pH 6.

Metabolomic study for the identification of symptomatic carotid plaque biomarkers.

Carotid artery stenosis is mainly produced due to the progressive accumulation of atherosclerotic plaque in the vascular wall. The atherosclerotic plaque is characterized by the accumulation of lipids, low density proteins, expression of chemokines and adhesion molecules, and migration of monocytes and lymphocytes into the plaque. Its rupture can produce stroke, but embolic propensity depends principally on the composition and vulnerability of plaque rather than the severity of stenosis.

Chemical Communication between Giant Vesicles and Gated Nanoparticles for Strip-Based Sensing.

Inspired by nature, the development of artificial micro/nanosystems capable of communicating has become an emergent topic in nanotechnology, synthetic biology, and related areas. However, the demonstration of actual applications still has to come. Here, we demonstrate how chemical communication between micro- and nanoparticles can be used for the design of sensing systems.

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.

Self-propelled enzyme-controlled IR-mesoporous silica Janus nanomotor for smart delivery.

Here, we report the preparation of a novel Janus nanoparticle with opposite Ir and mesoporous silica nanoparticles through a partial surface masking with toposelective modification method. This nanomaterial was employed to construct an enzyme-powered nanomachine with self-propulsion properties for on-command delivery. The cargo-loaded nanoparticle was provided with a pH-sensitive gate and unit control at the mesoporous face by first attaching boronic acid residues and further immobilization of glucose oxidase through reversible boronic acid esters with the carbohydrate residues of the glycoenzyme.

Water-Soluble Molecular Cages for Biological Applications.

The field of molecular cages has attracted increasing interest in relation to the development of biological applications, as evidenced by the remarkable examples published in recent years. Two key factors have contributed to this achievement: First, the remarkable and adjustable host-guest chemical properties of molecular cages make them highly suitable for biological applications. This allows encapsulating therapeutic molecules to improve their properties.

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.

Remarkable enhancement of cinnamaldehyde antimicrobial activity encapsulated in capped mesoporous nanoparticles: A new "nanokiller" approach in the era of antimicrobial resistance.

Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be approached using natural products, which have demonstrated powerful therapeutics against multidrug-resistant microbes. In the present work, a nanodevice consisting of mesoporous silica nanoparticles loaded with an essential oil component (cinnamaldehyde) and functionalized with the polypeptide ε-poly-l-lysine is developed and used as an antimicrobial agent.

Tear metabolomics for the diagnosis of primary open-angle glaucoma.

Primary Open-Angle Glaucoma (POAG) is the most prevalent glaucoma type, and the leading cause of irreversible visual impairment and blindness worldwide. Identification of early POAG biomarkers is of enormous value, as there is not an effective treatment for the glaucomatous optic nerve degeneration (OND). In this pilot study, a metabolomic analysis, by using proton (H) nuclear magnetic resonance (NMR) spectroscopy was conducted in tears, in order to determine the changes of specific metabolites in the initial glaucoma eyes and to discover potential diagnostic biomarkers.