Chondrocyte-targeted exosome-mediated delivery of Nrf2 alleviates cartilaginous endplate degeneration by modulating mitochondrial fission

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 24, 2024

Abstract Background Cartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead apoptosis during CEP IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis Despite their major success in drug delivery, full potential exosomes remains untapped. Materials methods In vitro vivo models were established using lipopolysaccharide (LPS). We designed genetically engineered (CAP-Nrf2-Exos) expressing chondrocyte-affinity peptide (CAP) on surface carrying antioxidant transcription factor nuclear E2-related 2 (Nrf2). The affinity between CAP-Nrf2-Exos was evaluated internalization assays imaging assays. qRT‒PCR, Western blotting immunofluorescence performed examine expression level Nrf2 subcellular localization Drp1. Mitochondrial function measured JC-1 probe MitoSOX Red. morphology visualized MitoTracker staining transmission electron microscopy (TEM). After subendplate injection exosomes, degree IVDD validated radiologically histologically. Results found cargo delivery efficiency after packaging increased modification. facilitated chondrocyte-targeted activated endogenous defence system cells. inhibited Drp1 S616 phosphorylation translocation, thereby preventing fragmentation dysfunction. LPS-induced cell alleviated CAP-Nrf2-Exo treatment. a rat model successfully attenuated exhibited better repair capacity than natural exosomes. Conclusion Collectively, our findings showed exosome-mediated effective strategy treating degeneration. Graphic abstract delivered into cells inhibiting Drp1-mediated

Язык: Английский

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Defining tropism and activity of natural and engineered extracellular vesicles

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 10, 2024

Extracellular vesicles (EVs) have important roles as mediators of cell-to-cell communication, with physiological functions demonstrated in various

Язык: Английский

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Extracellular vesicles transport RNA between cells: Unraveling their dual role in diagnostics and therapeutics

Molecular Aspects of Medicine, Год журнала: 2024, Номер 99, С. 101302 - 101302

Опубликована: Авг. 1, 2024

Modern methods of molecular diagnostics and therapy have revolutionized the field medicine in recent years by providing more precise effective tools for detecting treating diseases. This progress includes a growing exploration body's secreted vesicles, known as extracellular vesicles (EVs), both diagnostic therapeutic purposes. EVs are heterogeneous population lipid bilayer almost every cell type studied so far. They detected body fluids conditioned culture media from living cells. play crucial role communication between cells organs, locally over long distances. recognized their ability to transport endogenous RNA proteins cells, including messenger (mRNA), microRNA (miRNA), misfolded neurodegenerative proteins, several other biomolecules. review explores dual utilization EVs, serving not only purposes but also platform delivering molecules tissues. Through an composition, biogenesis, selective cargo packaging, we elucidate intricate mechanisms behind via highlighting potential use applications. Finally, it addresses challenges outlines prospective directions clinical EVs.

Язык: Английский

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Harnessing genetically engineered cell membrane-derived vesicles as biotherapeutics

Extracellular Vesicles and Circulating Nucleic Acids, Год журнала: 2024, Номер 5(1), С. 44 - 63

Опубликована: Янв. 30, 2024

Cell membrane-derived vesicles (CMVs) are particles generated from living cells, including extracellular (EVs) and artificial (aEVs) prepared cell membranes. CMVs possess considerable potential in drug delivery, regenerative medicine, immunomodulation, disease diagnosis,

Язык: Английский

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Most recent advances and applications of extracellular vesicles in tackling neurological challenges

Medicinal Research Reviews, Год журнала: 2024, Номер 44(4), С. 1923 - 1966

Опубликована: Март 18, 2024

Over the past few decades, there has been a notable increase in global burden of central nervous system (CNS) diseases. Despite advances technology and therapeutic options, neurological neurodegenerative disorders persist as significant challenges treatment cure. Recently, remarkable surge interest extracellular vesicles (EVs) pivotal mediators intercellular communication. As carriers molecular cargo, EVs demonstrate ability to traverse blood-brain barrier, enabling bidirectional result, they have garnered attention potential biomarkers agents, whether their natural form or after being engineered for use CNS. This review article aims provide comprehensive introduction EVs, encompassing various aspects such diverse isolation methods, characterization, handling, storage, different routes EV administration. Additionally, it underscores recent applications disorder therapeutics. By exploring unique capabilities, this study sheds light on promising future clinical research. It considers inherent limitations these emerging while incorporating most updates field.

Язык: Английский

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Magnetic Nanoparticle-Based Microfluidic Platform for Automated Enrichment of High-Purity Extracellular Vesicles

Analytical Chemistry, Год журнала: 2024, Номер 96(18), С. 7212 - 7219

Опубликована: Апрель 25, 2024

Extracellular vesicles (EVs) are available in various biological fluids and have highly heterogeneous sizes, origins, contents, functions. Rapid enrichment of high-purity EVs remains crucial for enhancing research on tumors. In this work, we present a magnetic nanoparticle-based microfluidic platform (ExoCPR) on-chip isolation, purification, mild recovery from cell culture supernatant plasma within 29 min. The ExoCPR chip integrates bubble-driven micromixers immiscible filtration assisted by surface tension (IFAST) technology. micromixer enhances the mixing between immunomagnetic beads EVs, eliminating need manual pipetting or off-chip oscillatory incubation. were obtained after passing through phase interface where hydrophilic hydrophobic impurities nonspecifically bound to SIMI removed. had capture efficiency 75.8% release 62.7% model EVs. We also demonstrated powerful performance isolating samples (>90% purity). This was further employed clinical showed that number GPC3-positive isolated hepatocellular carcinoma patients significantly higher than healthy individuals. may provide promising tool EV-based liquid biopsy other fundamental research.

Язык: Английский

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Endosomal escape mechanisms of extracellular vesicle-based drug carriers: lessons for lipid nanoparticle design

Extracellular Vesicles and Circulating Nucleic Acids, Год журнала: 2024, Номер 5(3), С. 344 - 57

Опубликована: Июль 5, 2024

The rise of biologics and RNA-based therapies challenges the limitations traditional drug treatments. However, these potent new classes therapeutics require effective delivery systems to reach their full potential. Lipid nanoparticles (LNPs) have emerged as a promising solution for RNA delivery, but endosomal entrapment remains critical barrier. In contrast, natural extracellular vesicles (EVs) possess innate mechanisms overcome degradation, demonstrating superior escape (EE) compared conventional LNPs. This mini review explores EE lipid nanoparticle-based offers insights into EV advance LNP design therapeutics. We compare strategies EVs with those used in LNPs highlight contemporary approaches. By understanding EE, we will be able develop more vehicles, enhancing efficacy therapies.

Язык: Английский

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Novel Endogenous Engineering Platform for Robust Loading and Delivery of Functional mRNA by Extracellular Vesicles

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Abstract Messenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a plethora of clinical applications. For in vivo functionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation reduce immunogenicity. Here, bioengineering platform efficient loading functional using bionormal nanoparticles, extracellular vesicles (EVs), is established by expressing highly specific RNA‐binding domain fused CD63 EV producer cells stably target mRNA. The additional combination with fusogenic endosomal escape moiety, Vesicular Stomatitis Virus Glycoprotein, enables at doses substantially lower than currently used clinically synthetic lipid‐based nanoparticles. Importantly, application EVs loaded effective cancer immunotherapy proves aggressive melanoma mouse model. This technology addresses substantial drawbacks associated EV‐based nucleic acid leap forward

Язык: Английский

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Exosomes in oral squamous cell carcinoma: functions, challenges, and potential applications

Frontiers in Oncology, Год журнала: 2025, Номер 14

Опубликована: Янв. 16, 2025

Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of all oral cancers, significantly impacting the survival and quality life patients. Exosomes, small extracellular vesicles released by cells, play a crucial role in intercellular communication cancer. Nevertheless, their function mechanism OSCC remain elusive. Search Pubmed, Web Science, Cochrane Library using keywords OSCC, exome, diagnosis, treatment to review research progress exome OSCC. Based on these results, this starting from biosynthesis, structure, contents exosomes, elaborates exosomes diagnosis It explores potential briefly describes challenges researchers currently face.

Язык: Английский

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Scalable production and purification of engineered ARRDC1-mediated microvesicles in a HEK293 suspension cell system

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 1, 2025

Abstract Engineering of human ARRDC1-mediated microvesicles (ARMMs) as non-viral vehicles for delivery gene therapies bears the potential to enable novel therapeutic paradigms. We evaluated two scalable strategies generate ARMMs loaded with protein cargo, by transient transfection or stable cell line-based production. The upstream production processes utilized a suspension-adapted HEK293-derived line, termed 5B8. 5B8 cells yielded robust after loading construct using line containing transgene that encodes cassette, in shake flasks stirred tank bioreactor, respectively. were purified ultracentrifugation (small scale) combination TFF and AEX (scalable production). Both purification methods produced comparable ARMMs, terms size payload incorporation. Single particle analysis showed approximately 50% payload-containing ARMMs. Additionally, an vivo study was conducted mice investigate half-life biodistribution administered intravenously. rapid predominantly spleen liver and, lesser extent, kidneys, lungs. plasma 6 ± 0.4 min. Altogether, this work advances knowledge on scale-up engineered cell-derived vesicles future molecules.

Язык: Английский

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