Cell-derived nanovesicle-mediated drug delivery to the brain: Principles and strategies for vesicle engineering

Molecular Therapy, Год журнала: 2022, Номер 31(5), С. 1207 - 1224

Опубликована: Окт. 17, 2022

Developing strategies toward safe and effective drug delivery into the central nervous system (CNS) with improved targeting abilities reduced off-target effects is crucial. CNS-targeted carriers made of synthetic molecules raise concerns about their biodegradation, clearance, immune responses, neurotoxicity. Cell-derived nanovesicles (CDNs) have recently been applied in delivery, because intrinsic stability, biocompatibility, inherent homing capability, ability to penetrate through biological barriers, including blood-brain barrier. Among these CDNs, extracellular vesicles exosomes are most studied surface can be engineered modified cater brain targeting. In this review, we focus on application CDNs brain-targeted treat neurological diseases. We cover developed methods exosome derivation engineering, exosome-like particles, hybrid exosomes, exosome-associated adeno-associated viruses, envelope protein nanocages. Finally, discuss limitations project future development CDN-based systems, conclude that hold great potential treatment

Язык: Английский

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Strategies for Targeted Delivery of Exosomes to the Brain: Advantages and Challenges

Pharmaceutics, Год журнала: 2022, Номер 14(3), С. 672 - 672

Опубликована: Март 18, 2022

Delivering therapeutics to the central nervous system (CNS) is difficult because of blood-brain barrier (BBB). Therapeutic delivery across tight junctions BBB can be achieved through various endogenous transportation mechanisms. Receptor-mediated transcytosis (RMT) one most widely investigated and used methods. Drugs hijack RMT by expressing specific ligands that bind receptors mediating transcytosis, such as transferrin receptor (TfR), low-density lipoprotein (LDLR), insulin (INSR). Cell-penetrating peptides viral components originating from neurotropic viruses also utilized for efficient crossing therapeutics. Exosomes, or small extracellular vesicles, have gained attention natural nanoparticles treating CNS diseases, owing their potential broad surface engineering capability. RMT-mediated transport exosomes LDLR-targeting apolipoprotein B has shown promising results. Although surface-modified possessing brain targetability enhanced in preclinical studies, successful development clinically approved exosome diseases requires establishment quantitative qualitative methods monitoring exosomal parenchyma vivo well elucidation mechanisms underlying exosomes.

Язык: Английский

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New strategies of neurodegenerative disease treatment with extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs)

Theranostics, Год журнала: 2023, Номер 13(12), С. 4138 - 4165

Опубликована: Янв. 1, 2023

Neurodegenerative diseases are characterized by the progressive loss of neurons and intricate interactions between different cell types within affected regions.Reliable biomarkers that can accurately reflect disease activity, diagnose, monitor progression neurodegenerative crucial for development effective therapies.However, identifying suitable has been challenging due to heterogeneous nature these diseases, affecting specific subsets in brain regions.One promising approach promoting regeneration recovery involves transplantation mesenchymal stem cells (MSCs).MSCs have demonstrated ability modulate immune system, promote neurite outgrowth, stimulate angiogenesis, repair damaged tissues, partially through release their extracellular vesicles (EVs).MSC-derived EVs retain some therapeutic characteristics parent MSCs, including regulate facilitate tissue repair.This review aims explore potential MSC-derived as an emerging strategy highlighting role modulating neuronal recovery.By elucidating mechanisms which exert effects, we advance our understanding leverage novel treatment approaches field diseases.

Язык: Английский

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Utility of Exosomes in Ischemic and Hemorrhagic Stroke Diagnosis and Treatment

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(15), С. 8367 - 8367

Опубликована: Июль 28, 2022

Stroke is the leading cause of death and neurological disorders worldwide. However, diagnostic techniques treatments for stroke patients are still limited certain types stroke. Intensive research has been conducted so far to find suitable treatments, but there no success. In recent years, various studies have drawn much attention clinical value utilizing mechanism exosomes, low toxicity, biodegradability, ability cross blood–brain barrier. Recent reported on use biomarkers protective recovery effects exosomes derived from stem cells or in stage after This review focuses publications describing changes following strokes processes potential applications as therapeutics.

Язык: Английский

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Bone marrow mesenchymal stem cell-derived exosomes carrying long noncoding RNA ZFAS1 alleviate oxidative stress and inflammation in ischemic stroke by inhibiting microRNA-15a-5p

Metabolic Brain Disease, Год журнала: 2022, Номер 37(7), С. 2545 - 2557

Опубликована: Июль 30, 2022

Язык: Английский

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Research Advances of Engineered Exosomes as Drug Delivery Carrier

ACS Omega, Год журнала: 2023, Номер 8(46), С. 43374 - 43387

Опубликована: Ноя. 9, 2023

Exosomes are nanoscale vesicles secreted by living cells that have similar membrane composition to parental and carry a variety of proteins, lipids, nucleic acids. Therefore, exosomes certain biological activities play an important role in intercellular communication. On the basis its potential as carrier for drug delivery systems, been engineered compensate shortage natural through various engineering strategies improving efficiency, enhancing targeting tissues organs, extending circulating half-life exosomes. This review focuses on loading drugs different strategies, discussions exosome surface modification summarizes advantages disadvantages strategies. In addition, this provides overview recent applications number refractory relapsable diseases. has provide reference further research development

Язык: Английский

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Exosomes in liver fibrosis: The role of modulating hepatic stellate cells and immune cells, and prospects for clinical applications

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 20, 2023

Liver fibrosis is a global health problem caused by chronic liver injury resulting from various factors. Hepatic stellate cells (HSCs) have been found to play major role in fibrosis, and pathological stimuli lead their transdifferentiation into myofibroblasts. Complex multidirectional interactions between HSCs, immune cells, cytokines are also critical for the progression of fibrosis. Despite advances treatments they do not meet current medical needs. Exosomes extracellular vesicles 30-150 nm diameter capable intercellular transport molecules such as lipids, proteins nucleic acids. As an essential mediator communication, exosomes involved physiological processes many diseases. In pathogenesis mainly regulating activation HSCs interaction cells. Serum-derived promising biomarkers therapeutic potential derived mesenchymal stem other exhibit anti-liver effects. Moreover, may serve targets hold promise becoming drug carriers treatment.

Язык: Английский

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Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 5863 - 5863

Опубликована: Май 28, 2024

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted progenitor stem cells have been associated with the therapeutic effects observed cell-based therapies, they also contribute to tissue regeneration following injury, such as orthopaedic surgery cases. This review explores involvement of nerve regeneration, their potential drug carriers, significance cell research cell-free therapies. It underscores importance bioengineers comprehending manipulating EV activity optimize efficacy engineering regenerative

Язык: Английский

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Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Ноя. 8, 2021

Macrophage phagocytosis contributes predominantly to processing central nervous system (CNS) debris and further facilitates neurological function restoration after CNS injury. The aims of this study were evaluate the effect bone marrow mesenchymal stem cells (BMSC)-derived exosomes (BMSC-Exos) on phagocytic capability macrophages clear myelin investigate underlying molecular mechanism during spinal cord injury (SCI) process. This work reveals that monocyte-derived (MDMs) infiltrating into SCI site could efficiently engulf process material. However, ability tissue is compromised SCI. administration BMSC-Exos as an approach for treatment rescue macrophage normal by improving internalization, which beneficial repair, evidenced better axon regrowth increased hindlimb locomotor functional recovery in a rodent model. Examination with revealed promote capacity phagocytose vitro create regenerative microenvironment regrowth. In addition, we confirmed BMSC-Exo resulted improved engulfed promoting expression receptor collagenous structure (MARCO) macrophages. inhibition MARCO PolyG (a antagonist) impaired clearance at lesion site, leading damage healing conclusion, these data indicated targeting may have therapeutic potential improvement cell-free immune therapy strategy has wide application prospects treatment.

Язык: Английский

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Potential Role of Exosomes in Ischemic Stroke Treatment

Biomolecules, Год журнала: 2022, Номер 12(1), С. 115 - 115

Опубликована: Янв. 11, 2022

Ischemic stroke is a life-threatening cerebral vascular disease and accounts for high disability mortality worldwide. Currently, no efficient therapeutic strategies are available promoting neurological recovery in clinical practice, except rehabilitation. The majority of neuroprotective drugs showed positive impact pre-clinical studies but failed trials. Therefore, there an urgent demand new promising approaches ischemic treatment. Emerging evidence suggests that exosomes mediate communication between cells both physiological pathological conditions. Exosomes have received extensive attention therapy following stroke, because their unique characteristics, such as the ability to cross blood brain–barrier, low immunogenicity, toxicity. An increasing number demonstrated positively neurorestorative effects exosome-based therapy, which largely mediated by microRNA cargo. Herein, we review current knowledge exosomes, relationships treatments neurovascular remodeling processes after stroke. provide viable prospective treatment strategy patients.

Язык: Английский

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