Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine

Pharmaceutics, Год журнала: 2024, Номер 16(6), С. 709 - 709

Опубликована: Май 24, 2024

Of all the numerous nanosized extracellular vesicles released by a cell, endosomal-originated exosomes are increasingly recognized as potential therapeutics, owing to their inherent stability, low immunogenicity, and targeted delivery capabilities. This review critically evaluates transformative of exosome-based modalities across pharmaceutical precision medicine landscapes. Because precise biomolecular cargo delivery, posited ideal candidates in drug enhancing regenerative strategies, advancing diagnostic technologies. Despite significant market growth projections exosome therapy, its utilization is encumbered substantial scientific regulatory challenges. These include lack universally accepted protocols for isolation complexities associated with navigating environment, particularly guidelines set forth U.S. Food Drug Administration (FDA). presents comprehensive overview current research trajectories aimed at addressing these impediments discusses prospective advancements that could substantiate clinical translation exosomal therapies. By providing analysis both capabilities hurdles therapeutic applications, this article aims inform direct future paradigms, thereby fostering integration systems into mainstream practice.

Язык: Английский

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Particle profiling of EV‐lipoprotein mixtures by AFM nanomechanical imaging

Journal of Extracellular Vesicles, Год журнала: 2023, Номер 12(10)

Опубликована: Окт. 1, 2023

The widely overlapping physicochemical properties of lipoproteins (LPs) and extracellular vesicles (EVs) represents one the main obstacles for isolation characterization these pervasive biogenic lipid nanoparticles. We herein present application an atomic force microscopy (AFM)-based quantitative morphometry assay to rapid nanomechanical screening mixed LPs EVs samples. method can determine diameter mechanical stiffness hundreds individual nanometric objects within few hours. obtained diameters are in accord with those measured via cryo-electron (cryo-EM); assignment specific readout each object enables simultaneous discrimination co-isolated even if they have size distributions. all classes shown be characterised by combinations stiffness, thus making it possible estimate their relative abundance EV/LP samples terms stoichiometric ratio, surface area volume. As a side finding, we show how behaviour LP is correlated distinctive structural features revealed cryo-EM. described approach label-free, single-step relatively quick perform. Importantly, used analyse which prove very challenging assess several established techniques due ensemble-averaging, low sensibility small particles, or both, providing useful tool quickly assessing purity isolates including plasma- serum-derived preparations.

Язык: Английский

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Label‐free discrimination of extracellular vesicles from large lipoproteins

Journal of Extracellular Vesicles, Год журнала: 2023, Номер 12(8)

Опубликована: Июль 25, 2023

Extracellular vesicles (EVs) are increasingly gaining interest as biomarkers and therapeutics. Accurate sizing quantification of EVs remain problematic, given their nanometre size range small scattering cross-sections. This is compounded by the fact that common EV isolation methods result in co-isolation particles with comparable features. Especially blood plasma, similarly-sized lipoproteins outnumber to a great extent. Recently, interferometric nanoparticle tracking analysis (iNTA) was introduced particle method enables determining refractive index nanoparticles high sensitivity precision. In this work, we apply iNTA differentiate between lipoproteins, compare its performance conventional (NTA). We show can accurately quantify artificial EV-lipoprotein mixtures plasma-derived samples varying complexity. Conventional NTA could not report on numbers, it able distinguish from lipoproteins. has potential become new standard for label-free characterization suspension.

Язык: Английский

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The physico-chemical landscape of extracellular vesicles

Nature Reviews Bioengineering, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 12, 2024

Язык: Английский

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Addressing Heterogeneity in Direct Analysis of Extracellular Vesicles and Their Analogs by Membrane Sensing Peptides as Pan‐Vesicular Affinity Probes

Advanced Science, Год журнала: 2024, Номер 11(29)

Опубликована: Май 31, 2024

Abstract Extracellular vesicles (EVs), crucial mediators of cell‐to‐cell communication, hold significant diagnostic potential due to their ability concentrate protein biomarkers in bodily fluids. However, challenges isolating EVs from biological specimens hinder widespread use. The preferred strategy involves direct analysis, integrating isolation and analysis solutions, with immunoaffinity methods currently dominating. Yet, the heterogeneous nature poses challenges, as proposed markers may not be universally present thought, raising concerns about biomarker screening reliability. This issue extends EV‐mimics, where conventional lack applicability. Addressing these study reports on Membrane Sensing Peptides (MSP) pan‐vesicular affinity ligands for both non‐canonical analogs, streamlining capture phenotyping through Single Molecule Array (SiMoA). MSP enable circulating EVs, eliminating need prior isolation. Demonstrating clinical translation, technology detects an EV‐associated epitope signature serum plasma, distinguishing myocardial infarction stable angina. Additionally, allow tetraspanin‐lacking Red Blood Cell‐derived overcoming limitations associated antibody‐based methods. Overall, work underlines value complementary tools antibodies, advancing EV diagnostics beyond, marking first‐ever peptide‐based application SiMoA technology.

Язык: Английский

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Azithromycin-loaded liposomes and niosomes for the treatment of skin infections: Influence of excipients and preparative methods on the functional properties

European Journal of Pharmaceutics and Biopharmaceutics, Год журнала: 2024, Номер 197, С. 114233 - 114233

Опубликована: Фев. 20, 2024

Язык: Английский

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Toward Clarity in Single Extracellular Vesicle Research: Defining the Field and Correcting Missteps

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Single extracellular vesicle (EV) research holds the potential to revolutionize our understanding of cellular communication and enable breakthroughs in diagnostics therapeutics. However, lack a clear, consensus-driven definition single EV has led methodological inconsistencies, overgeneralized interpretations, and, some cases, misleading claims. In this perspective, we propose framework for defining research, critique current challenges misconceptions field, discuss its implications biomedical applications. We argue that precise experimental design, rigorous validation, interdisciplinary collaboration approaches are needed establish as cornerstone precision medicine.

Язык: Английский

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Mucoadhesive polymer-coated liposomes as a promising approach to counteract bacteria responsible for aerobic vaginitis

International Journal of Pharmaceutics, Год журнала: 2025, Номер unknown, С. 125667 - 125667

Опубликована: Апрель 1, 2025

Aerobic vaginitis is an infectious disease characterized by the overgrowth of abnormal vaginal microflora. Conventional local dosage forms are not always effective, due to their inadequate drug release and residence time within cavity. Therefore, this study aimed develop azithromycin (AZT)-loaded liposomes, coated with two mucoadhesive polymers, chitosan (CS) sodium hyaluronate (HYA), increase thedrug's stay at site infection control its release. Liposomes were developed through thin film hydration method followed extrusion subsequently added polymer solution. Later, they size, surface charge, morphology, encapsulation efficiency. Furthermore, properties behavior investigated different pH values, e.g., 4.5 7.4, mimicking physiological pathological conditions, respectively. Finally, antimicrobial tests in vitro permeation studies carried out. Results showed size charge variations LP respect uncoated ones, confirming success coating process. possessed a good capacity encapsulate drug. Among all formulations, CS-LP demonstrated superior greatest both tested pHs, as well highest accumulation inside tissue, maintaining same AZT effect. Overall, could be proposed promising nanocarrier for delivery, virtue ability achieve locally sustained drug, helping lower administration frequency, consequently improving treatment efficacy.

Язык: Английский

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Bacterial extracellular vesicles as intranasal postbiotics: Detailed characterization and interaction with airway cells

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(10)

Опубликована: Окт. 1, 2024

Abstract Escherichia coli A0 34/86 (EcO83) is a probiotic strain used in newborns to prevent nosocomial infections and diarrhoea. This bacterium stimulates both pro‐ anti‐inflammatory cytokine production its intranasal administration reduces allergic airway inflammation mice. Despite benefits, there are concerns about the use of live bacteria due potential systemic gene transfer. Extracellular vesicles (EVs) derived from EcO83 (EcO83‐EVs) might offer safer alternative bacteria. study characterizes EcO83‐EVs investigates their interaction with host cells, highlighting as postbiotic therapeutics. were isolated, purified, characterised following Minimal Information Studies Vesicles (MISEV) guidelines. Ex vivo studies conducted human nasal epithelial cells showed that increased expression proteins linked oxidative stress inflammation, indicating an effective between EVs cells. Further mice demonstrated interact nasal‐associated lymphoid tissue, internalised by macrophages, stimulate neutrophil recruitment lung. Mechanistically, activate NF‐κΒ signalling pathway, resulting nitric oxide production. demonstrate significant bacteria, offering option for therapeutic applications. research required explore clinical use, particularly mucosal vaccination targeted immunotherapy strategies.

Язык: Английский

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Extracellular vesicles deliver functional extrachromosomal DNA in FGFR2-amplified cancer of unknown primary

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Background The extracellular vesicle (EV) pathway plays a critical role in cell-to-cell communication. Cancer cells release EVs into the space, where they interact with both cancerous and noncancerous cells, activating signaling pathways remodeling tumor microenvironment (TME). In this study, we investigated functional of released by FGFR2-amplified cancers unknown primary (CUPs), which generate extrachromosomal circular DNA (ecDNA) to enhance oncogenic amplification.Methods FGFR2 copy number was quantified using droplet digital PCR (ddPCR) visualized fluorescent situ hybridization (FISH). were isolated via ultracentrifugation, nature ecDNA assessed Plasmid-Safe ATP-dependent DNase treatment atomic force microscopy (AFM). Oncogene transfer through evaluated administering CUP-derived recipient NCI-N87 or coculture system that facilitated EV THP-1, HUVEC, fibroblast cell lines.Results FGFR2-containing ecDNA, is partially circular, packaged within exhibited activity upon delivery TME cells. When cancer (NCI-N87, THP-1) noncancer (HUVECs, fibroblasts) exposed EVs—either direct administration coculture—they internalized DNA, subsequently transcribed, leading altered morphology increased proliferation, depending on type. induced THP-1 polarization toward M2 macrophage subtype promoted HUVEC proliferation.Conclusion This mechanism oncogene can contribute remodeling, potentially explaining early metastatic potential CUP.

Язык: Английский

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