Exosome Drug Delivery through the Blood–Brain Barrier: Experimental Approaches and Potential Applications

Дружкова, Т. А.; Yakovlev, A. A.

doi:10.1134/s1819712418030030

Cited by 26 publications

(14 citation statements)

References 31 publications

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“…1 ) [ 44 , 45 ]. If the molecular mechanisms generating target cell tropism of exosomes is fully decoded, the potential of exosomes as a therapeutic vehicle would be greatly expanded, especially to the most challenging disease areas including the central nervous system (CNS) related diseases [ 46 ]. In this part, various factors that determine biodistribution and targetability of exosomes are discussed.…”

Section: Factors Modulating Biodistribution and Pk Of In Vivo Administered Exosomesmentioning

confidence: 99%

Biodistribution of Exosomes and Engineering Strategies for Targeted Delivery of Therapeutic Exosomes

Choi¹,

Choi²,

Yim³

et al. 2021

Tissue Eng Regen Med

123

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Exosomes are cell-secreted nano-sized vesicles which deliver diverse biological molecules for intercellular communication. Due to their therapeutic potential, exosomes have been engineered in numerous ways for efficient delivery of active pharmaceutical ingredients to various target organs, tissues, and cells. In vivo administered exosomes are normally delivered to the liver, spleen, kidney, lung, and gastrointestinal tract and show rapid clearance from the blood circulation after systemic injection. The biodistribution and pharmacokinetics (PK) of exosomes can be modulated by engineering various factors such as cellular origin and membrane protein composition of exosomes. Recent advances accentuate the potential of targeted delivery of engineered exosomes even to the most challenging organs including the central nervous system. Major breakthroughs have been made related to various imaging techniques for monitoring in vivo biodistribution and PK of exosomes, as well as exosomal surface engineering technologies for inducing targetability. For inducing targeted delivery, therapeutic exosomes can be engineered to express various targeting moieties via direct modification methods such as chemically modifying exosomal surfaces with covalent/non-covalent bonds, or via indirect modification methods by genetically engineering exosome-producing cells. In this review, we describe the current knowledge of biodistribution and PK of exosomes, factors determining the targetability and organotropism of exosomes, and imaging technologies to monitor in vivo administered exosomes. In addition, we highlight recent advances in strategies for inducing targeted delivery of exosomes to specific organs and cells.

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Section: Factors Modulating Biodistribution and Pk Of In Vivo Administered Exosomesmentioning

confidence: 99%

Biodistribution of Exosomes and Engineering Strategies for Targeted Delivery of Therapeutic Exosomes

Choi¹,

Choi²,

Yim³

et al. 2021

Tissue Eng Regen Med

123

View full text Add to dashboard Cite

show abstract

“…Therefore, many investigations, especially in the field of drug delivery, utilize both exosomes and microvesicles, in other words, EVs [ 17 ]. Actually, the natural role of EVs, responsible for intercellular communication, provides them with fundamental characteristics, exploitable for the formulation of drug delivery vehicles, like natural stability in blood and other biological fluids, and an intrinsic ability to cross biological barriers [ 18 , 19 ]. Furthermore, it was suggested that allogenic exosomes, collected from patients’ tissues and blood, should benefit from an immune-privileged status with low clearance by mononuclear phagocyte system and prolonged blood circulation [ 18 ].…”

mentioning

confidence: 99%

ZnO Nanocrystals Shuttled By Extracellular Vesicles As Effective Trojan nano-horses Against Cancer Cells

Dumontel

Susa

Limongi

et al. 2019

Nanomedicine (Lond.)

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Aim: The effective application of nanoparticles in cancer theranostics is jeopardized by their aggregation in biological media, rapid degradation and clearance. The design of biomimetic nanoconstructs with enhanced colloidal stability and non-immunogenicity is therefore essential. We propose naturally stable cell-derived extracellular vesicles to encapsulate zinc oxide (ZnO) nanocrystals as efficacious nanodrugs, to obtain highly biomimetic and stable Trojan nano-horses (TNHs). Materials & methods: Coupling efficiency, biostability, cellular cytotoxicity and internalization were tested. Results: In vitro studies showed a high internalization of TNHs into cancer cells and efficient cytotoxic activity thanks to ZnO intracellular release. Conclusion: TNHs represent an efficient biomimetic platform for future nanotheranostic applications, with biomimetic extracellular vesicle-lipid envelope, facilitated ZnO cellular uptake and potential therapeutic implications.

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“…These are small extracellular nanovesicles secreted by numerous cell [131,132]. Naturally-occurring extracellular vesicles such as exosomes traffic endogenous small molecules, proteins and nucleic acids between cells, [133,134] and they have shown considerable promise for the delivery of exogenous drugs or biological therapeutics, [135][136][137][138] including to the brain [139,140]. Exosomes have several advantages over synthetic NPs in that their biocompatibility confers upon them an inherent non-immunogenicity and long circulation times, however surface-functionalisation (e.g.…”

Section: Exosomesmentioning

confidence: 99%

Peptide based drug delivery systems to the brain

Islam

Leach

Smith³

et al. 2020

Nano Express

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With estimated worldwide cost over $1 trillion just for dementia, diseases of the central nervous system pose a major problem to health and healthcare systems, with significant socio-economic implications for sufferers and society at large. In the last two decades, numerous strategies and technologies have been developed and adapted to achieve drug penetration into the brain, evolving alongside our understanding of the physiological barriers between the brain and surrounding tissues. The blood brain barrier (BBB) has been known as the major barrier for drug delivery to the brain. Both invasive and minimally-invasive approaches have been investigated extensively, with the minimallyinvasive approaches to drug delivery being more suitable. Peptide based brain targeting has been explored extensively in the last two decades. In this review paper, we focused on self-assembled peptides, shuttle peptides and nanoparticles drug delivery systems decorated/conjugated with peptides for brain penetration.Abbreviations

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Exosome Drug Delivery through the Blood–Brain Barrier: Experimental Approaches and Potential Applications

Cited by 26 publications

References 31 publications

Biodistribution of Exosomes and Engineering Strategies for Targeted Delivery of Therapeutic Exosomes

Biodistribution of Exosomes and Engineering Strategies for Targeted Delivery of Therapeutic Exosomes

ZnO Nanocrystals Shuttled By Extracellular Vesicles As Effective Trojan nano-horses Against Cancer Cells

Peptide based drug delivery systems to the brain

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