The exosome journey: from biogenesis to uptake and intracellular signalling

Cell Communication and Signaling, Journal Year: 2021, Volume and Issue: 19(1)

Published: April 23, 2021

Abstract The use of exosomes in clinical settings is progressively becoming a reality, as trials testing for diagnostic and therapeutic applications are generating remarkable interest from the scientific community investors. Exosomes small extracellular vesicles secreted by all cell types playing intercellular communication roles health disease transferring cellular cargoes such functional proteins, metabolites nucleic acids to recipient cells. An in-depth understanding exosome biology therefore essential ensure development based investigational products. Here we summarise most up-to-date knowkedge about complex biological journey biogenesis secretion, transport uptake their intracellular signalling. We delineate major pathways molecular players that influence each step physiology, highlighting routes interest, which will be benefit manipulation engineering. highlight main controversies field research: adequate definition, characterisation at plasma membrane. also common identified pitfalls affecting research development. Unravelling physiology key ultimate progression towards applications.

Language: Английский

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Controlled Drug Delivery Systems: Current Status and Future Directions

Molecules, Journal Year: 2021, Volume and Issue: 26(19), P. 5905 - 5905

Published: Sept. 29, 2021

The drug delivery system enables the release of active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional systems (tablets, capsules, syrups, ointments, etc.) suffer from poor bioavailability and fluctuations in plasma level are unable sustained release. Without an efficient mechanism, whole process can be rendered useless. Moreover, has delivered at specified controlled rate target site as precisely possible maximum efficacy safety. Controlled developed combat problems associated with conventional delivery. There been tremendous evolution past two decades ranging macro scale nano intelligent targeted initial part this review provides basic understanding emphasis on pharmacokinetics drug. It also discusses their limitations. Further, discussed detail design considerations, classifications drawings. In addition, nano-drug delivery, smart using stimuli-responsive biomaterials is recent key findings. paper concludes challenges faced future directions

Language: Английский

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Engineering Macrophages for Cancer Immunotherapy and Drug Delivery

Advanced Materials, Journal Year: 2020, Volume and Issue: 32(40)

Published: Aug. 28, 2020

Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while anti-inflammatory M2 such as tumor-associated (TAMs) promote growth invasion. Modulating the immune microenvironment through engineering is efficacious therapy. target cancerous cells and, therefore, be used drug carriers for Herein, strategies to engineer immunotherapy, inhibition of macrophage recruitment, depletion TAMs, reprograming blocking CD47-SIRPα pathway, are discussed. Further, recent advances delivery using macrophages, macrophage-derived exosomes, macrophage-membrane-coated nanoparticles elaborated. Overall, there still significant room macrophage-mediated modulation delivery, which will further enhance current therapies against various malignant solid tumors, including drug-resistant tumors metastatic tumors.

Language: Английский

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A Review of Exosomal Isolation Methods: Is Size Exclusion Chromatography the Best Option?

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(18), P. 6466 - 6466

Published: Sept. 4, 2020

Extracellular vesicles (EVs) are membranous secreted by both prokaryotic and eukaryotic cells play a vital role in intercellular communication. EVs classified into several subtypes based on their origin, physical characteristics, biomolecular makeup. Exosomes, subtype of EVs, released the fusion multivesicular bodies (MVB) with plasma membrane cell. Several methods have been described literature to isolate exosomes from biofluids including blood, urine, milk, cell culture media, among others. While differential ultracentrifugation (dUC) has widely used exosomes, other techniques ultrafiltration, precipitating agents such as poly-ethylene glycol (PEG), immunoaffinity capture, microfluidics, size-exclusion chromatography (SEC) emerged credible alternatives pros cons associated each. In this review, we provide summary commonly exosomal isolation focus SEC an ideal methodology. We evaluate efficacy array biological fluids, particular its application adipose tissue-derived exosomes. argue that isolated via relatively pure functional, methodology is reproducible, scalable, inexpensive, does not require specialized equipment or user expertise. However, it must be noted while good candidate method direct comparative studies required support conclusion.

Language: Английский

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Comparative analysis of exosome isolation methods using culture supernatant for optimum yield, purity and downstream applications

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: March 29, 2019

Abstract Exosomes have received significant attention for their role in pathobiological processes and are being explored as a tool disease diagnosis management. Consequently, various isolation methods based on different principles been developed exosome isolation. Here we compared the efficacy of four kits from Invitrogen, 101Bio, Wako iZON along with conventional ultracentrifugation-based method yield, purity quality. Cell culture supernatant was used an abundant source exosomes, quantity, size-distribution, zeta-potential, marker-expression RNA/protein quality were determined. The Invitrogen kit gave highest yield but preparation showed broader size-distribution likely due to microvesicle co-precipitation had least dispersion stability. Other preparations <150 nm size range good Preparation column; however, lower suggestive some impurities non-vesicular aggregates. RNA all comparable; proteins method-based exosomal polyethylene glycol (PEG) contamination mass spectrometry. Chemical precipitant could also be cause toxicity biological growth measurement assay. Together, these findings should serve guide choose further optimize desired downstream applications.

Language: Английский

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Wound Healing: From Passive to Smart Dressings

Advanced Healthcare Materials, Journal Year: 2021, Volume and Issue: 10(16)

Published: June 26, 2021

Abstract The universal increase in the number of patients with nonhealing skin wounds imposes a huge social and economic burden on healthcare systems. Although, application traditional wound dressings contributes to an effective healing outcome, yet, complexity process remains major health challenge. Recent advances materials fabrication technologies have led that provide proper conditions for healing. 3D‐printed dressings, biomolecule‐loaded as well smart flexible bandages are among recent alternatives been developed accelerate Additionally, new generation contains variety microelectronic sensors real‐time monitoring environment is able apply required actions support progress. Moreover, manufacturing enable development next dressing substrates, known electronic skin, whole physiochemical markers single platform. current study reviews importance emerging strategy care management highlights different types promoting process.

Language: Английский

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Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Drug Delivery, Journal Year: 2020, Volume and Issue: 27(1), P. 585 - 598

Published: Jan. 1, 2020

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanosized membrane derived from most cell types. Carrying diverse biomolecules their parent cells, EVs important mediators of intercellular communication thus play significant roles in physiological pathological processes. Owing to natural biogenesis process, generated with high biocompatibility, enhanced stability, limited immunogenicity, which provide multiple advantages as drug delivery systems (DDSs) over traditional synthetic vehicles. have been reported be used for the siRNAs, miRNAs, protein, small molecule drugs, nanoparticles, CRISPR/Cas9 treatment various diseases. As a vectors, can penetrate into tissues bioengineered enhance targetability. Although EVs' characteristics make them ideal delivery, EV-based remains challenging, due lack standardized isolation purification methods, loading efficiency, insufficient clinical grade production. In this review, we summarized current knowledge on application DDS perspective different origin weighted bottlenecks DDS.

Language: Английский

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A review on exosomes application in clinical trials: perspective, questions, and challenges

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: Sept. 19, 2022

Abstract Background Exosomes are progressively known as significant mediators of cell-to-cell communication. They convey active biomolecules to target cells and have vital functions in several physiological pathological processes, show substantial promise novel treatment strategies for diseases. Methods In this review study, we studied numerous articles over the past two decades published on application exosomes different diseases well perspective challenges field. Results The main clinical using them a biomarker, cell-free therapeutic agents, drug delivery carriers, basic analysis exosome kinetics, cancer vaccine. Different from human or plant sources utilized various trials. Most researchers used circulatory system biomarker experiments. Mesenchymal stem (MSCs) dendritic (DCs) widely held cell use. MSCs-derived commonly inflammation delivery, while DCs-exosomes induce response patients. However, faces questions challenges. addition, translation exosome-based trials is required conform specific good manufacturing practices (GMP). review, summarize according type disease. We also address regarding kinetics applications. Conclusions promising platforms many This exciting field developing hastily, understanding underlying mechanisms that direct observed roles remains far complete needs further multidisciplinary research working with these small vesicles.

Language: Английский

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Macrophage-derived exosome-mimetic hybrid vesicles for tumor targeted drug delivery

Acta Biomaterialia, Journal Year: 2019, Volume and Issue: 94, P. 482 - 494

Published: May 24, 2019

Language: Английский

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Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine

Cells, Journal Year: 2021, Volume and Issue: 10(8), P. 1959 - 1959

Published: Aug. 1, 2021

Exosomes are a type of extracellular vesicles, produced within multivesicular bodies, that then released into the space through merging body with plasma membrane. These vesicles secreted by almost all cell types to aid in vast array cellular functions, including intercellular communication, differentiation and proliferation, angiogenesis, stress response, immune signaling. This ability contribute several distinct processes is due complexity exosomes, as they carry multitude signaling moieties, proteins, lipids, surface receptors, enzymes, cytokines, transcription factors, nucleic acids. The favorable biological properties exosomes biocompatibility, stability, low toxicity, proficient exchange molecular cargos make prime candidates for tissue engineering regenerative medicine. Exploring functions payloads can facilitate regeneration therapies provide mechanistic insight paracrine modulation activities. In this review, we summarize current knowledge exosome biogenesis, composition, isolation methods. We also discuss emerging healing exosomal cargos, such microRNAs, brain injuries, cardiovascular disease, COVID-19 amongst others. Overall, review highlights burgeoning roles potential applications

Language: Английский

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