Enhanced Tumor Site Accumulation and Therapeutic Efficacy of Extracellular Matrix‐Drug Conjugates Targeting Tumor Cells

Small, Год журнала: 2024, Номер unknown

Опубликована: Июнь 3, 2024

Abstract The extracellular matrix (ECM) engages in regulatory interactions with cell surface receptors through its constituent proteins and polysaccharides. Therefore, nano‐sized conjugated doxorubicin (DOX) is utilized to produce matrix‐drug conjugates (ECM‐DOX) tailored for targeted delivery cancer cells. ECM‐DOX nanoparticles exhibit rod‐like morphology, boasting a commendable drug loading capacity of 4.58%, coupled acid‐sensitive release characteristics. Notably, enhance the uptake by tumor cells possess ability penetrate endothelial infiltrate multicellular spheroids. Mechanistic insights reveal that internalization nanoparticle facilitated clathrin‐mediated endocytosis macropinocytosis, intricately involving hyaluronic acid integrins. Pharmacokinetic assessments unveil prolonged blood half‐life at 3.65 h, substantial improvement over 1.09 h observed free DOX. A sustained accumulation effect sites, levels tissues surpassing those DOX several‐fold. profound therapeutic impact evident their notable inhibition growth, extension median survival time animals, significant reduction DOX‐induced cardiotoxicity. ECM platform emerges as promising carrier avant‐garde nanomedicines realm treatment.

Язык: Английский

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From gut to liver: organoids as platforms for next-generation toxicology assessment vehicles for xenobiotics

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Март 26, 2025

Traditional toxicological assessment relied heavily on 2D cell cultures and animal models of study, which were inadequate for the precise prediction human response to chemicals. Researchers have now shifted focus organoids assessment. Organoids are 3D structures produced from stem cells that mimic shape functionality organs a number advantages compared traditional study. They capacity replicate intricate cellular microenvironment in vivo interactions. offer physiologically pertinent platform is useful researchers monitor responses more realistic manner evaluate drug toxicity. Additionally, can be created unique patient, allowing individualized research providing understanding inter-individual heterogeneity responses. Recent developments use gut liver xenobiotics (environmental toxins drugs) reviewed this article. Gut reveal potential damage digestive system how affect nutrient absorption barrier function. Liver primary site detoxification metabolism xenobiotics, usually routed gut. Hence, these linked crucial evaluating chemical or pollutant induced organ toxicity, forecasting their pharmacokinetics. When incorporated into development process, organoid improve accuracy efficiency safety assessments, leading safer effective treatments. We also discuss limitations using organoid-based assays, future prospects, including need standardized protocols overcoming reproducibility issues.

Язык: Английский

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Liver‐on‐a‐Chip Integrated with Label‐Free Optical Biosensors for Rapid and Continuous Monitoring of Drug‐Induced Toxicity

Small, Год журнала: 2024, Номер unknown

Опубликована: Авг. 30, 2024

Drug toxicity assays using conventional 2D static cultures and animal studies have limitations preventing the translation of potential drugs to clinic. The recent development organs-on-a-chip platforms provides promising alternatives for drug toxicity/screening assays. However, most conducted with these only utilize single endpoint results, which do not provide real-time/ near real-time information. Here, a versatile technology is presented that integrates 3D liver-on-a-chip label-free photonic crystal-total internal reflection (PC-TIR) biosensor rapid continuous monitoring status cells. This can detect drug-induced liver by continuously secretion rates levels albumin glutathione S-transferase α (GST-α) on-a-chip model treated Doxorubicin. PC-TIR based on one-step antibody functionalization high specificity detection range 21.7 ng mL

Язык: Английский

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Exploiting the Potential of Decellularized Extracellular Matrix (ECM) in Tissue Engineering: A Review Study

Macromolecular Bioscience, Год журнала: 2024, Номер 25(1)

Опубликована: Окт. 16, 2024

Abstract While significant progress has been made in creating polymeric structures for tissue engineering, the therapeutic application of these scaffolds remains challenging owing to intricate nature replicating conditions native organs and tissues. The use human‐derived biomaterials purposes closely imitates properties natural tissue, thereby assisting regeneration. Decellularized extracellular matrix (dECM) derived from tissues have become popular because their unique biomimetic properties. These dECM can enhance body's ability heal itself or be used generate new restoration, expanding beyond traditional transfers transplants. Enhanced knowledge how ECM scaffold materials affect microenvironment at injury site is expected improve clinical outcomes. In this review, recent advancements are explored relevant perspectives offered, highlighting development engineering various organs, such as skin, nerve, bone, heart, liver, lung, kidney.

Язык: Английский

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Decellularized extracellular matrix-based disease models for drug screening

Materials Today Bio, Год журнала: 2024, Номер 29, С. 101280 - 101280

Опубликована: Сен. 28, 2024

Язык: Английский

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