Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury

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

Опубликована: Июль 1, 2024

Abstract Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to myocardium. This phenomenon known as ischemia-reperfusion (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) play a significant role in regulating immune response has been studied its potential impact on improvement function injury. However, delivery miR-146a specific efficient manner remains challenge extracellular RNAs are unstable rapidly degraded. Milk exosomes (MEs) have proposed ideal platform miRNA-based they protect miRNAs from RNase degradation. In this study, effects containing MEs (MEs-miR-146a) cardiac were examined rat model MIRI. To enhance targeting MEs-miR-146a site injury, ischemic myocardium-targeted peptide IMTP was modified onto surfaces, whether could exert better therapeutic by echocardiography, indicators levels inflammatory factors. Furthermore, expressions mediated NF-κB signaling pathway-related proteins detected western blotting qRT-PCR elucidate mechanisms. MiR-146 mimics successfully loaded into electroporation at square wave 1000 V voltage 0.1 ms pulse duration. be up-taken cardiomyocytes protected cells oxygen glucose deprivation/reperfusion induced damage vitro. Oral administration decreased tissue apoptosis expression factors improved The level myocardium tissues significantly increased MEs-miR-146a, higher than that group. addition, intravenous injection enhanced heart, function, reduced suppressed inflammation MIRI, more effective treatment. Moreover, protein IRAK1, TRAF6 p-p65. Therefore, exerted their anti-inflammatory effect inhibiting IRAK1/TRAF6/NF-κB pathway. Taken together, our findings suggested may promising strategy treatment MIRI with outcome modification peptide, expected applied clinical practice future.

Язык: Английский

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Engineered and Mimicked Extracellular Nanovesicles for Therapeutic Delivery

Nanomaterials, Год журнала: 2024, Номер 14(7), С. 639 - 639

Опубликована: Апрель 6, 2024

Exosomes are spherical extracellular nanovesicles with an endosomal origin and unilamellar lipid-bilayer structure sizes ranging from 30 to 100 nm. They contain a large range of proteins, lipids, nucleic acid species, depending on the state vesicle (EV)-secreting cell. EVs’ function is encapsulate part EV-producing cell content, transport it through biological fluids targeted recipient, deliver their cargos specifically within aimed recipient cells. Therefore, exosomes considered be potential drug-delivery systems that can stably cargo into Various cell-derived produced for medical issues, but use therapeutic purposes still faces several problems. Some these difficulties avoided by resorting hemisynthetic approaches. We highlight here uses alternative exosome-mimes involving cell-membrane coatings artificial nanocarriers or hybridization between liposomes. also detail drug-loading strategies deployed make them drug-carrier summarize ongoing clinical trials exosome-like structures. Finally, we open questions before considering disposals confident delivery.

Язык: Английский

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Unravelling exosome paradigm: Therapeutic, diagnostic and theranostics application and regulatory consideration

Life Sciences, Год журнала: 2025, Номер unknown, С. 123472 - 123472

Опубликована: Фев. 1, 2025

Язык: Английский

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Exosomes as new generation vehicles for drug delivery systems

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 95, С. 105562 - 105562

Опубликована: Март 11, 2024

Язык: Английский

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Different origin-derived exosomes and their clinical advantages in cancer therapy

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июнь 27, 2024

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior various types tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding diagnosis, stability their membrane structure wide distribution body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor future. For treatment, exosomes, “golden communicators” between cells, can be designed deliver different drugs, aiming achieve low-toxicity low-immunogenicity targeted delivery. Signaling pathways exosome contents also used safer more effective immunotherapy against tumors. Exosomes derived from range sources, exhibit characteristics well clinical application advantages therapies. In this review, we analyzed main sources have great potential broad prospects therapy. Moreover, compared therapeutic advantages, providing new ideas exosomes.

Язык: Английский

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Milk exosomes: Harnessing nature's duality for cancer therapy

Clinical and Translational Discovery, Год журнала: 2024, Номер 4(4)

Опубликована: Июль 19, 2024

Abstract Milk exosomes, extracellular nanovesicles that are naturally present in milk, have gained significant attention cancer research for their potential to revolutionize treatment strategies. They possess a specific set of characteristics make them promising nanoscale vehicles targeted drug delivery systems. Their inherent biocompatibility, coupled with ability effectively encapsulate and transport therapeutic agents directly into tumor cells, suggests the possibility developing novel therapies, potentially minimizing side effects associated conventional therapies. However, recent studies shown milk exosomes dual nature, which is not entirely positive. Although they show delivering anticancer therapeutics, evidence may also, under certain conditions, contribute progression. This paradoxical nature necessitates better understanding how interact work different stages cancer. Further investigation crucial understand factors influencing behaviour develop strategies can maximize prospects while mitigating risks use treatment.

Язык: Английский

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Drug Delivery Systems Based on Dendritic-Cell-Derived Exosomes

Pharmaceutics, Год журнала: 2025, Номер 17(3), С. 326 - 326

Опубликована: Март 3, 2025

Exosomes, spherical lipid-bilayered particles secreted by cells, have recently emerged as a novel and highly promising drug delivery system, attracting extensive attention in the field of biomedical research. Dendritic-cell-derived exosomes (DC-Exos) possess surface protein ligands characteristic DC such functional MHC-I MHC-II, CD80, CD86. These components play crucial role immune responses, facilitating antigen uptake, presentation, activation antigen-specific CD4 CD8 T cells. properties make them striking excellent vehicles for use various diseases cancer therapy. This review summarizes discusses characteristics, current methods types loading DC-Exos. Its modifications application disease treatment were also discussed, aiming to motivate development exosome-based theranostic nanoplatforms nanotechnology improved healthcare treatments.

Язык: Английский

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Exosomes in Precision Oncology and Beyond: From Bench to Bedside in Diagnostics and Therapeutics

Cancers, Год журнала: 2025, Номер 17(6), С. 940 - 940

Опубликована: Март 10, 2025

Exosomes have emerged as pivotal players in precision oncology, offering innovative solutions to longstanding challenges such metastasis, therapeutic resistance, and immune evasion. These nanoscale extracellular vesicles facilitate intercellular communication by transferring bioactive molecules that mirror the biological state of their parent cells, positioning them transformative tools for cancer diagnostics therapeutics. Recent advancements exosome engineering, artificial intelligence (AI)-driven analytics, isolation technologies are breaking barriers scalability, reproducibility, clinical application. Bioengineered exosomes being leveraged CRISPR-Cas9 delivery, while AI models enhancing biomarker discovery liquid biopsy accuracy. Despite these advancements, key obstacles heterogeneity populations lack standardized protocols persist. This review synthesizes pioneering research on biology, molecular translation, emphasizing dual roles both mediators tumor progression intervention. It also explores emerging areas, including microbiome–exosome interactions integration machine learning exosome-based medicine. By bridging innovation with translational strategies, this work charts a forward-looking path integrating into next-generation care, setting it apart comprehensive guide overcoming technological hurdles rapidly evolving field.

Язык: Английский

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Proteomic Profiling of Donkey Milk Exosomes Highlights Bioactive Proteins with Immune-Related Functions

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2892 - 2892

Опубликована: Март 22, 2025

The growing recognition of the role milk-derived exosomes in metabolic and immunological processes has brought attention to potential utility donkey milk. However, efficacy bioactive components milk are underexplored. This study aimed elucidate proteomic profiles isolated from colostrum mature using advanced four-dimensional (4D) label-free quantitative proteomics. A comprehensive analysis identified quantified a total 2293 exosomal proteins milk, including 276 differentially expressed (DEEPs). results revealed marked differences between exosomes, particularly associated with immune responses pathways. Exosomal derived were found be enriched immune-modulatory factors glycan-related pathways, which may contribute enhancement neonatal system development. In contrast, predominantly cellular senescence. Protein-protein interaction (PPI) further suggested that specific highly could serve as nutraceutical health benefits for humans. conclusion, this underscores distinct features physiological roles versus

Язык: Английский

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Development and In Vitro Characterization of Milk-Derived Extracellular Vesicle-Mithramycin Formulations for Potential Glioma Therapy

Molecular Pharmaceutics, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Glioblastoma (GBM) is a highly aggressive brain tumor with resistance to conventional therapies. Mithramycin (Mit-A), potent antitumor agent, has shown promise in several types including, GBM. However, its clinical application limited by toxicity. To address this, we explored the use of milk-derived extracellular vesicles (mEVs) as delivery system enhance therapeutic efficacy Mit-A. In this study, mEVs were isolated using 3000 PEG precipitation method and confirmed their size, morphology, stability through dynamic light scattering (DLS), transmission electron microscopy (TEM), atomic force (AFM). The size 125.6 ± 2.78 nm, polydispersity index (PDI) 0.083 0.02, ζ-potential 15 0.57 mV. presence typical EV markers such TSG101, HSP70, CD63 purity. Encapsulation Mit-A within led slight increase 131.8 6.9 PDI 0.081 0.006, decrease −17 2.0 mV, an encapsulation efficiency 58% freeze–thaw method. vitro transepithelial transport assay revealed that mEV(Mit-A) transported more effectively than free formulation demonstrated excellent simulated salivary gastrointestinal fluids, sustained release observed over 24 h PBS (pH 6.8). Furthermore, formulations significantly inhibited glioma cell growth, migration, induced apoptosis, showing 2-fold lower IC50 Mit-A, indicating superior efficacy. These findings suggest represent promising vehicle for enhancing potential effective treatment glioblastoma.

Язык: Английский

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