Leveraging nature’s nanocarriers: Translating insights from extracellular vesicles to biomimetic synthetic vesicles for biomedical applications

Science Advances, Journal Year: 2025, Volume and Issue: 11(9)

Published: Feb. 26, 2025

Naturally occurring extracellular vesicles (EVs) and synthetic nanoparticles like liposomes have revolutionized precision diagnostics medicine. EVs excel in biocompatibility cell targeting, while offer enhanced drug loading capacity scalability. The clinical translation of is hindered by challenges including low yield heterogeneity, whereas face rapid immune clearance limited targeting efficiency. To bridge these gaps, biomimetic (SVs) emerged as innovative platforms, combining the advantageous properties liposomes. This review emphasizes critical aspects EV biology, such mechanisms EV-cell interaction source-dependent functionalities modulation, tissue regeneration, informing SV engineering. We reviewed a broad array SVs, with focus on lipid bilayered functionalized proteins. These include cell-derived nanovesicles, protein-functionalized liposomes, hybrid vesicles. By addressing current highlighting opportunities, this aims to advance SVs for transformative biomedical applications.

Language: Английский

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Migrasome: a new functional extracellular vesicle

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Oct. 18, 2023

Abstract Migrasome is a novel cellular organelle produced during cell migration, and its biogenesis depends on the migration process. It generated in variety of cells such as immune cells, metastatic tumor other special functional like podocytes developing organisms. plays important roles various fields especially information exchange between cells. The discovery migrasome, an supplement to extracellular vesicle system, provides new mechanisms targets for comprehending biological or pathological processes. In this article, we will review discovery, structure, distribution, detection, biogenesis, removal migrasomes mainly focus summarizing functions cell-to-cell communication, homeostatic maintenance, embryonic development multiple diseases. This also creates prospects possible research directions clinical applications future.

Language: Английский

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CRISPR-Cas9 delivery strategies with engineered extracellular vesicles

Molecular Therapy — Nucleic Acids, Journal Year: 2023, Volume and Issue: 34, P. 102040 - 102040

Published: Sept. 26, 2023

Therapeutic genome editing has the potential to cure diseases by directly correcting genetic mutations in tissues and cells. Recent progress CRISPR-Cas9 systems led breakthroughs gene tools because of its high orthogonality, versatility, efficiency. However, safe effective administration target organs patients is a major hurdle. Extracellular vesicles (EVs) are endogenous membranous particles secreted spontaneously all They key actors cell-to-cell communication, allowing exchange select molecules such as proteins, lipids, RNAs induce functional changes recipient Recently, EVs have displayed their for trafficking system during or after formation. In this review, we highlight recent developments EV loading, surface functionalization, strategies increasing efficiency delivering tissues, organs, cells eventual use therapies.

Language: Английский

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CD151-enriched migrasomes mediate hepatocellular carcinoma invasion by conditioning cancer cells and promoting angiogenesis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: June 6, 2024

Abstract Background The tetraspanin family plays a pivotal role in the genesis of migrasomes, and Tetraspanin CD151 is also implicated neovascularization within tumorous contexts. Nevertheless, research pertaining to involvement hepatocellular carcinoma (HCC) its association with migrasomes remains inadequate. Methods To investigate correlation between migrasome marker TSPAN4 liver cancer, we conducted database analysis using clinical data from HCC patients. Expression levels were assessed tissues correlated patient survival outcomes. In vitro experiments performed cell lines evaluate impact expression on formation cellular invasiveness. Cell altered utilized study generation invasion capabilities. Additionally, function was explored through aggregation assays phagocytosis studies. Subsequent VEGF level tissue chip further confirmed mediating angiogenesis signal transduction. Results Our revealed significant based samples. High closely associated poor outcomes Experimentally, decreased led reduced diminished capabilities, resulting attenuated vivo metastatic potential. Migrasomes demonstrated facilitate phagocytosis, thereby promoting Furthermore, VEGF-enriched signaling angiogenesis, accelerating progression. Conclusions summary, our findings support notion that elevated promotes formation, play invasiveness cancer cells, facilitating This finding implies generated by may constitute promising high-priority target for anti-angiogenic therapy HCC, offering crucial insights in-depth exploration renewed comprehension mechanism underlying metastasis.

Language: Английский

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Mitocytosis Mediated by an Enzyme‐Activable Mitochondrion‐Disturbing Polymer‐Drug Conjugate Enhances Active Penetration in Glioblastoma Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(18)

Published: Feb. 1, 2024

The application of nanomedicines for glioblastoma (GBM) therapy is hampered by the blood-brain barrier (BBB) and dense tissue. To achieve efficient BBB crossing deep GBM penetration, this work demonstrates a strategy active transcellular transport mitochondrion-disturbing nanomedicine, pGBEMA

Language: Английский

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Emerging role of extracellular vesicles in diabetic retinopathy

Theranostics, Journal Year: 2024, Volume and Issue: 14(4), P. 1631 - 1646

Published: Jan. 1, 2024

Diabetic retinopathy (DR), a complex complication of diabetes mellitus (DM), is leading cause adult blindness.Hyperglycemia triggers DR, resulting in microvascular damage, glial apoptosis, and neuronal degeneration.Inflammation oxidative stress play crucial roles during this process.Current clinical treatments for DR primarily target the advanced retinal disorder but offer limited benefits with inevitable side effects.Extracellular vesicles (EVs) exhibit unique morphological features, contents, biological properties can be found cell culture supernatants, various body fluids, tissues.In EVs specific cargo composition would induce reaction receptor once internalized, mediating cellular communication disease progression.Increasing evidence indicates that monitoring changes EV quantity content aid diagnosis prognosis.Furthermore, extensive research investigating potential these nanoparticles as effective therapeutic agents preclinical models DR.This review explores current understanding pathological effects development, discusses their biomarkers strategies, paves way further advancements.

Language: Английский

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Glioblastoma-derived migrasomes promote migration and invasion by releasing PAK4 and LAMA4

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 20, 2025

Almost all high-grade gliomas, particularly glioblastoma (GBM), are highly migratory and aggressive. Migrasomes organelles produced by cells capable of mediating intercellular communication. Thus, GBM may produce migrasomes during migration. However, it remains unclear whether can influence migration invasion. In this study, we observed the presence formation in cells. We found that expression levels key migrasome factor, tetraspanin 4 (TSPAN4), correlated positively with pathological grade poor prognosis based on databases clinical samples analysis. Subsequently, knocked down TSPAN4 cell invasion were significantly inhibited due to reduced migrasomes. further confirmed enriched extracellular matrix (ECM)-related proteins such as p21-activating kinase (PAK4) laminin alpha (LAMA4). Our experimental results suggest promote releasing into space. Overall, identified molecular mechanisms which they regulate them, providing potential targets for treating GBM. Observation (GBM) analysis migrasome-enriched revealed matrix-associated PAK4 LAMA4.

Language: Английский

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Migrasomes derived from human umbilical cord mesenchymal stem cells: a new therapeutic agent for ovalbumin-induced asthma in mice

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 26, 2025

Asthma is a prevalent respiratory disease, and its management remains largely unsatisfactory. Mesenchymal stem cells (MSCs) have been demonstrated to be efficacious in reducing airway inflammation experimental allergic diseases, representing potential alternative treatment for asthma. Migrasomes are recently identified extracellular vesicles (EVs) generated migrating facilitate intercellular communication. The objective of this study was investigate the therapeutic effects migrasomes obtained from MSC model produced by human umbilical cord MSCs (hUCMSCs) were isolated sequential centrifugation. Characterization hUCMSC-derived carried out transmission electron microscopy western blot analysis. on ovalbumin (OVA)-induced asthmatic mice evaluated hematoxylin-eosin (HE) periodic-acid schiff (PAS) staining, their mechanism further testified immunofluorescent real-time PCR flow cytometry. Here, we showed that inhibition migrasomes' production dramatically impaired anti-inflammatory hUCMSCs OVA animals, as evidenced notable increase both infiltration inflammatory number epithelial goblet cells. We successfully hUCMSC-migrasomes, which morphologically intact positive specific markers. administration hUCMSC-migrasomes observed significantly ameliorate symptoms mucus mice. Additionally, expression Th2 cytokines (IL-4, IL-5 IL-13) found reduced, while activation dendritic (DCs) inhibited. HUCMSC-migrasomes could possibly delivered lung region after injection, able taken DCs vivo vitro. Notably, vitro, migraosmes decreased capacity BMDCs stimulate OVA-specific Th2-cell responses. More importantly, adoptive transfer hUCMSC-migrasomes-treated sufficient protect inflammation. In addition, inhibited receptor advanced glycation end-products (RAGE) signal OVA-treated vitro asthma vivo. Our results provided first evidence possess properties OVA-induced mice, may provide novel "MSC-cell free" agent

Language: Английский

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On the road: extracellular vesicles in intercellular communication

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 18, 2025

Cells from organisms across all kingdoms of life continuously release a diverse repertoire extracellular vesicles (EVs) into their environment as an elegant strategy for both, cellular homeostasis and communication with other cells. Through different biogenesis routes within the donor cell, nanosized are generated either endomembranes or plasma membrane, loaded decorated macromolecular cargo in controlled manner through molecular sorting machineries. Since they can affect recipient cell same tissue, distant organs even organisms, EVs have been increasingly recognized essential mediators orchestrating intercellular health disease. In last 15 years, research on fundamental biology well potential biomedical applications has greatly intensified. Time to present new advances EV biogenesis, competencies technical special thematic series Cell Communication Signaling.

Language: Английский

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Young fibroblast-derived migrasomes alleviate keratinocyte senescence and enhance wound healing in aged skin

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 11, 2025

Abstract Background Alterations in intercellular communication driven by cellular senescence constitute an important factor skin aging. Migrasome, a newly discovered vesicular organelle, efficiently participates communication; however, the relationship between and migrasomes remains unreported. Objective This study aims to explore possible formation, investigate effects of young fibroblast-derived on senescent keratinocytes wound healing aged skin. Result Single-cell RNA sequencing (scRNA-seq) data analysis revealed that fibroblasts exhibited highest level transcriptional variability during aging, degree fibroblast negatively correlated with expression migrasome-associated markers. Further multiplex Immunohistochemistry (mIHC) results suggested younger mouse contained more than older Transmission electron microscopy (TEM) observations demonstrated abundant from individuals. In vitro experiments indicated produced significantly fibroblasts, as confirmed wheat germ agglutinin (WGA) staining scanning (SEM). Importantly, purified were found reduce senescence-associated markers HaCaT cells. vivo, using model naturally mice, we observed derived not only accelerated but also reduced marker Conclusion Migrasomes formation ability aging progress, rejuvenated promoted These findings offer new ideas for alleviating enhancing Graphical abstract

Language: Английский

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