The Machinery of Exosomes: Biogenesis, Release, and Uptake

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1337 - 1337

Published: Jan. 10, 2023

Exosomes are a subtype of membrane-contained vesicles 40–200 nm in diameter that secreted by cells into their surroundings. By transporting proteins, lipids, mRNA, miRNA, lncRNA, and DNA, exosomes able to perform such vital functions as maintaining cellular homeostasis, removing debris, facilitating intercellular interorgan communication. travel all body fluids deliver molecular messages autocrine, paracrine well endocrine manners. In recent years, there has been an increased interest studying diagnostic markers therapeutic targets, since many disease conditions this machinery becomes dysregulated or hijacked pathological processes. Additionally, delivery exosomal miRNA already shown improve systemic metabolism inhibit progression cancer development mice. However, the subcellular exosomes, including biogenesis, release uptake, remains largely unknown. This review will bring details these processes up date with goal expanding knowledge basis for designing impactful exosome experiments future.

Language: Английский

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Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(1), P. 122 - 122

Published: Jan. 19, 2021

Since the 2013 Nobel Prize was awarded for discovery of vesicle trafficking, a subgroup nanovesicles called exosomes has been driving research field to new regime understanding cellular communication. This exosome-dominated traffic control system increased many diseases, including cancer metastasis, diabetes, and HIV. In addition important diagnostic role, are particularly attractive drug delivery, due their distinctive properties in information transfer uptake. Compared viral non-viral synthetic systems, natural, cell-derived exhibit intrinsic payload bioavailability. Most importantly, easily cross biological barriers, obstacles that continue challenge other delivery nanoparticle systems. Recent emerging studies have shown numerous critical roles blood–brain barrier (BBB), blood–cerebrospinal fluid (BCSFB), blood–lymph (BlyB), blood–air (BAB), stromal (SB), blood–labyrinth (BLaB), blood–retinal (BRB), placental (PB), which opens exciting possibilities using as platform. However, systematic reviews summarizing such discoveries still limited. review covers state-of-the-art exosome on crossing several barriers with focus current, accepted models used explain mechanisms crossing, tight junctions. The potential design engineer enhance efficacy, leading future applications precision medicine immunotherapy, is discussed.

Language: Английский

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Extracellular vesicles through the blood–brain barrier: a review

Fluids and Barriers of the CNS, Journal Year: 2022, Volume and Issue: 19(1)

Published: July 25, 2022

Abstract Extracellular vesicles (EVs) are particles naturally released from cells that delimited by a lipid bilayer and unable to replicate. How the EVs cross Blood–Brain barrier (BBB) in bidirectional manner between bloodstream brain parenchyma remains poorly understood. Most vitro models have evaluated this event relied on monolayer transwell or microfluidic organ-on-a-chip techniques do not account for combined effect of all cellular layers constitute BBB at different sites Central Nervous System. There has been direct transcytosis visualization through mammals vivo, evidence comes vivo experiments zebrafish. Literature is scarce topic, describing mechanisms motion inconsistent. This review will focus methodologies used evaluate transcytosis, how overcome fundamental structure, discuss potential methodological approaches future analyses clarify these issues. Understanding be essential their use as vehicles pharmacology therapeutics.

Language: Английский

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Exosome-Based Smart Drug Delivery Tool for Cancer Theranostics

ACS Biomaterials Science & Engineering, Journal Year: 2023, Volume and Issue: 9(2), P. 577 - 594

Published: Jan. 9, 2023

Exosomes are the phospholipid-membrane-bound subpopulation of extracellular vesicles derived from plasma membrane. The main activity exosomes is cellular communication. In cancer, play an important rolefrom two distinct perspectives, one related to carcinogenesis and other as theragnostic drug delivery tools. outer phospholipid membrane Exosome improves targeting efficiency. . Some vital features such biocompatibility, low toxicity, immunogenicity make it a more exciting system. Exosome-based new innovative approach cancer treatment. Exosome-associated biomarker analysis heralded era diagnostics in specific way. This Review focuses on exosome biogenesis, sources, isolation, interrelationship with exosome-related biomarkers, loading methods, exosome-based biomolecule delivery, advances limitations clinical settings studies. understanding will change diagnostic therapeutic future.

Language: Английский

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Development of Novel Therapeutics Targeting the Blood–Brain Barrier: From Barrier to Carrier

Advanced Science, Journal Year: 2021, Volume and Issue: 8(16)

Published: June 3, 2021

Abstract The blood–brain barrier (BBB) is a highly specialized neurovascular unit, initially described as an intact to prevent toxins, pathogens, and potentially harmful substances from entering the brain. An BBB also critical for maintenance of normal neuronal function. In cerebral vascular diseases neurological disorders, can be disrupted, contributing disease progression. While restoration integrity serves robust biomarker better clinical outcomes, restrictive nature presents major hurdle delivery therapeutics into Recent studies show that actively engaged in crosstalk between circulatory systems, which defines another important role BBB: interfacing conduit mediates communication two sides BBB. This has been subject extensive investigation brain‐targeted drug shows promising results. dual roles make it unique target development. Here, recent developments novel strategies therapeutic purposes are reviewed, both carrier perspectives.

Language: Английский

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Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Sept. 20, 2021

Extracellular vesicles (EVs) hold great promise as therapeutic modalities due to their endogenous characteristics, however, further bioengineering refinement is required address clinical and commercial limitations. Clinical applications of EV-based therapeutics are being trialed in immunomodulation, tissue regeneration recovery, delivery vectors for combination therapies. Native/biological EVs possess diverse properties that offer stability facilitate crossing biological barriers molecular cargo cells, acting a form intercellular communication regulate function phenotype. Moreover, important components paracrine signaling stem/progenitor cell-based therapies, employed standalone can be used drug system. Despite remarkable utility native/biological EVs, they improved using bio/engineering approaches potential. engineered harbor specific pharmaceutical content, enhance stability, modify surface epitopes tropism targeting cells tissues vivo. Limitations currently challenging the full realization include scalability standardization generation, characterization design regulation, potency assessment, targeted delivery. The fields' utilization advanced technologies (imaging, quantitative analyses, multi-omics, labeling/live-cell reporters), biocompatible natural sources producing (plants, bacteria, milk) will play an role overcoming these Advancements EV engineering methodologies development therapeutics, revolutionizing current landscape.

Language: Английский

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Exosomes based strategies for brain drug delivery

Biomaterials, Journal Year: 2022, Volume and Issue: 293, P. 121949 - 121949

Published: Dec. 8, 2022

Language: Английский

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Insight into Extracellular Vesicle-Cell Communication: From Cell Recognition to Intracellular Fate

Cells, Journal Year: 2022, Volume and Issue: 11(9), P. 1375 - 1375

Published: April 19, 2022

Extracellular vesicles (EVs) are heterogamous lipid bilayer-enclosed membranous structures secreted by cells. They comprised of apoptotic bodies, microvesicles, and exosomes, carry a range nucleic acids proteins that necessary for cell-to-cell communication via interaction on the cells surface. initiate intracellular signaling pathways or transference cargo molecules, which elicit pleiotropic responses in recipient physiological processes, as well pathological such cancer. It is therefore important to understand molecular means EVs taken up into Accordingly, this review summarizes underlying mechanisms involved EV targeting uptake. The primary method entry appears be endocytosis, where clathrin-mediated, caveolae-dependent, macropinocytotic, phagocytotic, raft-mediated uptake have been variously described being prevalent. may depend lipids found surfaces both target As shown contribute cancer growth progression, further exploration gateways utilized internalize tumor assist prevention deceleration pathogenesis.

Language: Английский

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Specific anti‐glioma targeted‐delivery strategy of engineered small extracellular vesicles dual‐functionalised by Angiopep‐2 and TAT peptides

Journal of Extracellular Vesicles, Journal Year: 2022, Volume and Issue: 11(8)

Published: Aug. 1, 2022

Glioma is one of the primary malignant brain tumours in adults, with a poor prognosis. Pharmacological reagents targeting glioma are limited to achieve desired therapeutic effect due presence blood-brain barrier (BBB). Effectively crossing BBB and specifically tumour major challenge for treatments. Here, we demonstrate that well-defined small extracellular vesicles (sEVs) dual-targeting drug delivery cell-penetrating functions, modified by Angiopep-2 trans-activator transcription peptides, enable efficient specific chemotherapy glioma. The high efficiency engineered sEVs was assessed both monolayer culture cells model vitro, respectively. observed re-validated subcutaneous orthotopic mice models. After loading doxorubicin into dual-modified functional sEVs, this system could cross BBB, reach glioma, penetrate tumour. Such mode significantly improved more than 2-fold survival time very few side effects. In conclusion, utilization represents unique strategy delivery, holding great promise treatments central nervous diseases.

Language: Английский

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Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis

Theranostics, Journal Year: 2022, Volume and Issue: 12(3), P. 1220 - 1246

Published: Jan. 1, 2022

Background: Obesity is becoming a global epidemic and reversing the pathological processes underlying obesity metabolic co-morbidities challenging.Obesity induced chronic inflammation including brain hallmark of via gut-brain axis.The objective this study was to develop garlic exosome-like nanoparticles (GaELNs) that inhibit systemic as well inflammatory activity reverse HFD in mice.Methods: GELNs were isolated administrated orally into fed mice.GaELNs fluorescent labeled for monitoring their vivo trafficking route after oral administration quantified number particles several tissues.The determined by measuring cytokines ELISA real-time PCR.Mitochondrial membrane permeability microglial cells using JC-10 fluorescence dye.The apoptotic cell death TUNEL assay.The metabolites identified LC-MS analysis.Memory function mice memory functional analysis.The effect GaELNs on glucose insulin response tolerance tests.c-Myc localization interaction with BASP1 calmodulin confocal microscopy.Results: Our results show preferentially taken up inhibits mice.GaELN phosphatidic acid (PA) (36:4) required uptake BASP1.Formation GaELNs/BASP1 complex inhibition c-Myc mediated expression STING.GaELN PA binds BASP1, leading through competitively binding CaM transcription factor.Inhibition STING leads reducing an array IFN-γ TNF-α.IFN-γ induces IDO1, which turn generated IDO1 dependent manner activate AHR pathway contributes developing obesity.The derived from treated promote neuronal differentiation mitochondrial death.GaELNs showed improved increased sensitivity these mice.Conclusion: Collectively, demonstrate how healthy diet can unhealthy high-fat reveal link between microglia/diet disease outcomes diet-derived nanoparticles.

Language: Английский

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