Recent advances in exosome-mediated nucleic acid delivery for cancer therapy

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: June 14, 2022

Abstract Cancer is a leading public health problem worldwide. Its treatment remains daunting challenge, although significant progress has been made in existing treatments recent years. A large concern the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy recently emerged as powerful tool for cancer therapy. However, delivery methods limit its effects. Exosomes, subset extracellular vesicles secreted by most cells, have characteristics good biocompatibility, toxicity immunogenicity, great designability. In past decades, carriers diagnostic markers, they caught extensive attention. This review introduced exosomes, focused on their applications DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering (siRNA), circular (circRNA) other nucleic acids. Meanwhile, application exosome-based clinical trials were presented discussed. Through systematic summarization analysis, advances current challenges exosome-mediated acid are introduced, which will provide theoretical basis development drugs. Graphical

Language: Английский

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Current Strategies for Exosome Cargo Loading and Targeting Delivery

Cells, Journal Year: 2023, Volume and Issue: 12(10), P. 1416 - 1416

Published: May 17, 2023

Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer are secreted by various cells. Due their high biocompatibility, stability, low immunogenicity, favored cargo carriers. The membrane of also offers protection against degradation, making them desirable candidate However, loading into remains be challenge. Despite strategies incubation, electroporation, sonication, extrusion, freeze–thaw cycling, transfection that been developed facilitate loading, inadequate efficiency still persists. This review an overview current delivery using summarizes recent approaches small-molecule, nucleic acid, protein drugs exosomes. With insights these studies, we provide ideas more efficient effective molecules

Language: Английский

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Extracellular vesicle‐mediated delivery of circDYM alleviates CUS‐induced depressive‐like behaviours

Journal of Extracellular Vesicles, Journal Year: 2022, Volume and Issue: 11(1)

Published: Jan. 1, 2022

Abstract Major depressive disorder (MDD) is the most prevalent psychiatric worldwide and severely limits psychosocial function quality of life, but no effective medication currently available. Circular RNAs (circRNAs) have been revealed to participate in MDD pathological process. Targeted delivery circRNAs without blood‐brain barrier (BBB) restriction for remission represents a promising approach antidepressant therapy. In this study, RVG‐circDYM‐extracellular vesicles (RVG‐circDYM‐EVs) were engineered target preferentially transfer circDYM brain, effect on process chronic unpredictable stress (CUS) mouse model depression was investigated. The results showed that RVG‐circDYM‐EVs successfully purified by ultracentrifugation from overexpressed HEK 293T cells, characterization demonstrated terms size, morphology specific markers. Beyond demonstrating proof‐of‐concept an RNA drug technology, we observed systemic administration efficiently delivered alleviated CUS‐induced depressive‐like behaviours, discovered notably inhibited microglial activation, BBB leakiness peripheral immune cells infiltration, attenuated astrocyte disfunction induced CUS. CircDYM can bind mechanistically transcription factor TAF1 (TATA‐box binding protein associated 1), resulting decreased expression its downstream genes with consequently suppressed neuroinflammation. Taken together, our findings suggest extracellular vesicle‐mediated treatment clinical applications.

Language: Английский

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

Molecular Therapy, Journal Year: 2022, Volume and Issue: 31(5), P. 1207 - 1224

Published: Oct. 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

Language: Английский

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Nucleic acid drug vectors for diagnosis and treatment of brain diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 17, 2023

Abstract Nucleic acid drugs have the advantages of rich target selection, simple in design, good and enduring effect. They been demonstrated to irreplaceable superiority brain disease treatment, while vectors are a decisive factor therapeutic efficacy. Strict physiological barriers, such as degradation clearance circulation, blood-brain barrier, cellular uptake, endosome/lysosome release, obstruct delivery nucleic by vectors. against single inefficient treating diseases complex pathogenesis. Differences between individual patients lead severe uncertainties treatment with drugs. In this Review, we briefly summarize classification Next, discuss barriers during drug universal coping strategies introduce application methods these Subsequently, explore drug-based multidrug regimens for combination construction corresponding following, address feasibility patient stratification personalized therapy through diagnostic information from medical imaging manner introducing contrast agents into Finally, take perspective on future remaining challenges vector-based integrated diagnosis gene diseases.

Language: Английский

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Targeted therapy using engineered extracellular vesicles: principles and strategies for membrane modification

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 16, 2023

Abstract Extracellular vesicles (EVs) are 30–150 nm membrane-bound naturally secreted by cells and play important roles in intercellular communication delivering regulatory molecules such as proteins, lipids, nucleic acids metabolites to recipient cells. As natural nano-carriers, EVs possess desirable properties high biocompatibility, biological barrier permeability, low toxicity, immunogenicity, making them potential therapeutic delivery vehicles. derived from specific have inherent targeting capacity towards cell types, which is yet not satisfactory enough for targeted therapy development needs be improved. Surface modifications endow with abilities, significantly improving their efficiency. Herein, we first briefly introduce the biogenesis, composition, uptake function of EVs, review cargo loading approaches EVs. Then, summarize recent advances surface engineering strategies focusing on applications engineered therapy. Altogether, hold great promise various cargos, show promising effects multiple diseases. Graphical

Language: Английский

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Gut microbiota-derived short-chain fatty acids and depression: deep insight into biological mechanisms and potential applications

General Psychiatry, Journal Year: 2024, Volume and Issue: 37(1), P. e101374 - e101374

Published: Feb. 1, 2024

The gut microbiota is a complex and dynamic ecosystem known as the ‘second brain’. Composing microbiota-gut-brain axis, its metabolites regulate central nervous system through neural, endocrine immune pathways to ensure normal functioning of organism, tuning individuals’ health disease status. Short-chain fatty acids (SCFAs), main bioactive microbiota, are involved in several neuropsychiatric disorders, including depression. SCFAs have essential effects on each component axis In present review, roles major (acetate, propionate butyrate) pathophysiology depression summarised with respect chronic cerebral hypoperfusion, neuroinflammation, host epigenome neuroendocrine alterations. Concluding remarks biological mechanisms related will hopefully address clinical value microbiota-related treatments for

Language: Английский

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Engineered EVs designed to target diseases of the CNS

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 356, P. 493 - 506

Published: March 15, 2023

Diseases of the central nervous system (CNS) are challenging to treat, mainly due blood-brain barrier (BBB), which restricts drugs in circulation from entering target regions brain. To address this issue extracellular vesicles (EVs) have gained increasing scientific interest as carriers able cross BBB with multiplex cargos. EVs secreted by virtually every cell, and their escorted biomolecules part an intercellular information gateway between cells within brain other organs. Scientists undertaken efforts safeguard inherent features therapeutic delivery vehicles, such protecting transferring functional cargo, well loading them small molecules, proteins, oligonucleotides targeting specific cell types for treatment CNS diseases. Here, we review current emerging approaches that engineer EV surface cargo improve responses We summarize existing applications engineered a platform diseases, some been evaluated clinically.

Language: Английский

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Noteworthy perspectives on microglia in neuropsychiatric disorders

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Oct. 4, 2023

Abstract Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood–brain barrier architecture, and intriguingly, the regulation of emotions behaviors. have a profound impact on neuronal survival, wiring synaptic plasticity. As professional phagocytic cells brain, remove dead cell debris neurotoxic agents via an elaborate mechanism. The functional profile microglia varies considerately depending age, gender, disease context other internal or external environmental factors. Numerous studies demonstrated pivotal involvement neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain symptoms associated with major depression disorder, anxiety autism spectrum disorder schizophrenia. In this review, we summarized latest discoveries regarding microglial ontogeny, subtypes state spectrum, biological functions mechanistic underpinnings emotional behavioral disorders. Furthermore, highlight potential microglia-targeted therapies propose outstanding questions to be addressed future research human microglia.

Language: Английский

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Extracellular vesicle‐based nucleic acid delivery

Deleted Journal, Journal Year: 2023, Volume and Issue: 1(2)

Published: Jan. 15, 2023

Abstract Extracellular vesicles (EVs) are a heterogeneous class of natural that facilitate intercellular communication by functional transfer lipids and biomolecular cargoes, such as miRNAs, mRNAs proteins. As naturally occurring delivery vehicle for nucleic acids, EVs characterized multiple advantageous characteristics, unique size structure, excellent biocompatibility, immunologically inert, increased stability in circulation, intrinsic targeting capacity the capability membrane fusion crossing biological barriers. Of note, properties can be further improved genetic engineering donor cells or direct modification EVs. Over last decade, have sparkled intensive interest small RNAs, including interfering RNAs (siRNAs) microRNAs (miRNAs). In recent years, increasing attention has been focused on exploring variety strategies to harness more acid types. present perspective, we provide capsule overview latest accomplishments trends field EV‐based systems siRNAs, messenger (mRNAs), clustered regularly interspaced short palindromic repeats‐associated endonuclease (CRISPR/Cas) systems, antisense oligonucleotides (ASOs), circular RNA (circRNAs), long noncoding (lncRNAs) DNAs. This perspective may offer insights into rational design cutting‐edge extracellular vesicle‐based nanoplatforms.

Language: Английский

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