Bridging Smart Nanosystems with Clinically Relevant Models and Advanced Imaging for Precision Drug Delivery

Advanced Science, Journal Year: 2024, Volume and Issue: 11(14)

Published: Jan. 28, 2024

Abstract Intracellular delivery of nano‐drug‐carriers (NDC) to specific cells, diseased regions, or solid tumors has entered the era precision medicine that requires systematic knowledge nano‐biological interactions from multidisciplinary perspectives. To this end, review first provides an overview membrane‐disruption methods such as electroporation, sonoporation, photoporation, microfluidic delivery, and microinjection with merits high‐throughput enhanced efficiency for in vitro NDC delivery. The impact characteristics including particle size, shape, charge, hydrophobicity, elasticity on cellular uptake are elaborated several types systems aiming hierarchical targeting vivo reviewed. Emerging ex human/animal‐derived pathophysiological models further explored highly recommended use studies since they might mimic features fill translational gaps animals humans. exploration modern microscopy techniques precise nanoparticle (NP) tracking at cellular, organ, organismal levels informs tailored development NDCs application clinical translation. Overall, integrates latest insights into smart nanosystem engineering, physiological models, imaging‐based validation tools, all directed towards enhancing efficient intracellular NDCs.

Language: Английский

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Safe and sustainable by design of next generation chemicals and materials: SSbD4CheM project innovations in the textiles, cosmetic and automotive sectors

Computational and Structural Biotechnology Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

The strategic objective of the Safe and sustainable by design next generation chemicals materials (SSbD4CheM) project is to develop screening testing strategies for a variety substances ensure safer more products in line with Sustainable Products Initiative. SSbD4CHeM focusing on chemical safety using new approach methods, including vitro studies without animal models silico tools. Additionally, it integrates environmental sustainability implementation Design (SSbD) framework risk assessment ex-ante life cycle assessment. New methods along chemical, material product cycles will be developed, validated, applied three case studies, biobased self-cleaning, water repellent, antimicrobial treatments textiles, nanocellulose as an additive cosmetics, microcellulose composites automotive industry. By employing multidisciplinary strategy, addresses key challenges innovation, ensuring regulatory compliance while reducing hazards human health. accelerate development next-generation materials, promoting industry progress, improved consumer safety. Ultimately, SSbD4CheM aims establish benchmark that conform goals.

Language: Английский

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Optimization of a micro-scale air–liquid-interface model of human proximal airway epithelium for moderate throughput drug screening for SARS-CoV-2

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 16, 2025

Many respiratory viruses attack the airway epithelium and cause a wide spectrum of diseases for which we have limited therapies. To date, few primary human stem cell-based models proximal been reported drug discovery but scaling them up to higher throughput platform remains significant challenge. As result, most screening assays are performed on commercial cell line-based 2D cultures that provide translational ability. We optimized mucociliary model SARS-CoV-2 infection, in 96-well air-liquid-interface (ALI) format, is amenable moderate screening. tested against parental strain (Wuhan) variants Beta, Delta, Omicron. applied this screen 2100 compounds from targeted libraries using high throughput-high content image-based quantification method. The recapitulated heterogeneity infection among patients with variants. While there were heterogeneous responses across host factor targeting compounds, two direct-acting antivirals tested, Remdesivir Paxlovid, showed consistent efficacy reducing all donors. Using model, characterized new antiviral effective both Omicron variant. This study demonstrates ALI can recapitulate different donors be used Compounds target factors variability response SARS-CoV-2, while despite tested.

Language: Английский

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Advanced in vitro systems available for respiratory toxicology

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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High Throughput Screening with a Primary Human Mucociliary Airway Model Identifies a Small Molecule with Anti-SARS-CoV-2 Activity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 10, 2024

Summary Respiratory viruses (e.g. influenza, RSV, SARS etc.) attack the proximal airway and cause a wide spectrum of diseases for which we have limited therapies. To date, few primary human stem cell-based models been reported drug discovery but scaling them up to higher throughput platform remains significant challenge. Here present microscale, model SARS-CoV-2 infection, is amenable moderate-to-high screening. The recapitulates heterogeneity infection seen among different patients with variants. We applied this screen 2100 compounds from targeted libraries using an image-based quantification method. While there were heterogeneous responses across variants host factor targeting compounds, direct acting antivirals showed consistent response characterized new antiviral that effective against both parental strain Omicron variant.

Language: Английский

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The ENDOMIX project: an interdisciplinary approach to understanding how real-life chemical mixtures target the immune system to trigger disease

Open Research Europe, Journal Year: 2024, Volume and Issue: 4, P. 271 - 271

Published: Dec. 19, 2024

The true impact of endocrine disrupting chemicals (EDCs) on human health is far from being understood. Humans are exposed to mixtures throughout their lives, yet regulations and most studies focus individual chemicals. ENDOMIX takes a novel approach identifying associations causality between EDCs adverse outcomes by focusing exposure over the life course, including windows susceptibility, using biomonitoring data several European cohorts. We will model measure how real-life EDC act together target immune system initiate, trigger or maintain disease. Health effects be investigated pioneering methodologies ranging high-throughput in vitro bioassays, sophisticated organoid co-culture systems, vivo models. In combination, they provide valuable information mechanistic pathways transgenerational exposure. aim identify biomarkers patterns chemical exposures that easy measure, available for large cohorts indicative outcomes. use vitro, silico strengthen causal inference weight-of-evidence approach. Moreover, text mining methods, we create knowledge graphs capture summarize complexity biomechanistic information, which aids rapid risk assessments creation network The generated an evidence base policy-making also reach people all ages raise awareness risks encourage health-promoting behaviors.

Language: Английский

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Occupationally Relevant Zinc‐ and Copper‐Containing Metal Fumes Inhibit Human THP‐1 Macrophage TNF and IL‐6 Responses to Bacterial Stimuli

Global Challenges, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 31, 2024

Metal workers have an increased risk of severe lobar pneumonia due to exposure metal fume particles, which lead recent pneumococcal vaccination recommendations. To investigate the effects fume-derived zinc oxide (ZnO) and copper (CuO) particles on airway immune responses, human THP-1-derived macrophages are exposed in vitro bacterial pathogen-associated molecular patterns (PAMPs) lipopolysaccharide (LPS), lipoteichoic Acid (LTA), or peptidoglycan (PGN), together with particle suspensions. Particles generated through inert gas (MIG) soldering. Spectrometric microscopic analysis confirms CuO ZnO as main components. Macrophage IL-6 TNF mRNAs quantified by qPCR secreted protein levels electrochemiluminescent multi-spot assay. A dose-dependent increase macrophage mRNA (4 h) (24 following PAMPs is significantly inhibited 2 µg mL-1 CuO/ZnO (n = 5). Additionally, inhibit expression unstimulated macrophages, while unaffected The presented immunotoxicity approach may extend existing new methodology (NAM) elements for chemical assessment possibly limit evaluation refinements. These findings implicate that suppress proinflammatory responses PAMPs, potentially compromising lung immunity, underlining current vaccine recommendations efforts preventive occupational health guidelines.

Language: Английский

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