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微小RNA纳米穿梭体:将细胞外囊泡工程化为用于治疗的前沿临床生物技术平台。

MicroRNA Nano-Shuttles: Engineering Extracellular Vesicles as a Cutting-Edge Biotechnology Platform for Clinical Use in Therapeutics.

作者信息

Menjivar Nico G, Oropallo Jaiden, Gebremedhn Samuel, Souza Luca A, Gad Ahmed, Puttlitz Christian M, Tesfaye Dawit

机构信息

Animal Reproduction and Biotechnology Laboratory (ARBL), Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, 80523, USA.

Orthopaedic Bioengineering Research Laboratory (OBRL), Translational Medicine Institute (TMI), Department of Mechanical Engineering, Colorado State University, Fort Collins, CO, 80523, USA.

出版信息

Biol Proced Online. 2024 May 21;26(1):14. doi: 10.1186/s12575-024-00241-6.


DOI:10.1186/s12575-024-00241-6
PMID:38773366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11106895/
Abstract

Extracellular vesicles (EVs) are nano-sized, membranous transporters of various active biomolecules with inflicting phenotypic capabilities, that are naturally secreted by almost all cells with a promising vantage point as a potential leading drug delivery platform. The intrinsic characteristics of their low toxicity, superior structural stability, and cargo loading capacity continue to fuel a multitude of research avenues dedicated to loading EVs with therapeutic and diagnostic cargos (pharmaceutical compounds, nucleic acids, proteins, and nanomaterials) in attempts to generate superior natural nanoscale delivery systems for clinical application in therapeutics. In addition to their well-known role in intercellular communication, EVs harbor microRNAs (miRNAs), which can alter the translational potential of receiving cells and thus act as important mediators in numerous biological and pathological processes. To leverage this potential, EVs can be structurally engineered to shuttle therapeutic miRNAs to diseased recipient cells as a potential targeted 'treatment' or 'therapy'. Herein, this review focuses on the therapeutic potential of EV-coupled miRNAs; summarizing the biogenesis, contents, and function of EVs, as well as providing both a comprehensive discussion of current EV loading techniques and an update on miRNA-engineered EVs as a next-generation platform piloting benchtop studies to propel potential clinical translation on the forefront of nanomedicine.

摘要

细胞外囊泡(EVs)是纳米级的膜性转运体,可运输各种具有表型影响能力的活性生物分子,几乎所有细胞都会自然分泌EVs,作为一种潜在的领先药物递送平台,它具有广阔的应用前景。其低毒性、卓越的结构稳定性和货物装载能力等内在特性,持续推动着众多研究方向,致力于将治疗性和诊断性货物(药物化合物、核酸、蛋白质和纳米材料)装载到EVs中,试图打造出更优质的天然纳米级递送系统,用于临床治疗。除了在细胞间通讯中发挥的众所周知的作用外,EVs还携带微小RNA(miRNAs),这些miRNAs可以改变受体细胞的翻译潜能,从而在众多生物和病理过程中充当重要的介质。为了利用这一潜能,可以对EVs进行结构工程改造,将治疗性miRNAs转运到患病的受体细胞,作为一种潜在的靶向“治疗”手段。在此,本综述聚焦于EVs偶联miRNAs的治疗潜力;总结EVs的生物发生、内容物和功能,同时全面讨论当前的EVs装载技术,并更新关于miRNA工程化EVs的研究进展,其作为一个下一代平台正在引领基础研究,推动纳米医学前沿领域的潜在临床转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/11106895/a83db6623eb3/12575_2024_241_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/11106895/4b20f688b72f/12575_2024_241_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/11106895/57f3bf098a9c/12575_2024_241_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/11106895/2333f4880c40/12575_2024_241_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/11106895/a83db6623eb3/12575_2024_241_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/11106895/4b20f688b72f/12575_2024_241_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/11106895/57f3bf098a9c/12575_2024_241_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/11106895/2333f4880c40/12575_2024_241_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b0e/11106895/a83db6623eb3/12575_2024_241_Fig4_HTML.jpg

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引用本文的文献

[1]
The Role of Extracellular Vesicles in Mediating Signaling in Biliary Epithelial Cell Activation and Cholangiopathies.

Cells. 2025-8-18

[2]
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[3]
MSC-derived extracellular vesicles: Precision miRNA delivery for overcoming cancer therapy resistance.

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[4]
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[5]
Unlocking Gamete Quality Through Extracellular Vesicles: Emerging Perspectives.

Biology (Basel). 2025-2-13

[6]
Effects of Replicative Senescence of Human Chorionic MSCs on their EV-miRNA Profile.

Stem Cell Rev Rep. 2024-11

本文引用的文献

[1]
Unpacking extracellular vesicles: RNA cargo loading and function.

J Extracell Biol. 2022-5-2

[2]
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.

J Extracell Vesicles. 2024-2

[3]
Bovine oviductal organoids: a multi-omics approach to capture the cellular and extracellular molecular response of the oviduct to heat stress.

BMC Genomics. 2023-10-27

[4]
Extracellular vesicle-microRNAs mediated response of bovine ovaries to seasonal environmental changes.

J Ovarian Res. 2023-5-23

[5]
Granulosa cell-derived extracellular vesicles mitigate the detrimental impact of thermal stress on bovine oocytes and embryos.

Front Cell Dev Biol. 2023-4-6

[6]
Dynamics of extracellular vesicle-coupled microRNAs in equine follicular fluid associated with follicle selection and ovulation.

Mol Hum Reprod. 2023-4-3

[7]
Micro RNA based MSC EV engineering: Targeting the BMP2 cascade for bone repair.

Front Cell Dev Biol. 2023-2-8

[8]
New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment.

Int J Mol Sci. 2022-12-12

[9]
Combinatorial microRNA Loading into Extracellular Vesicles for Increased Anti-Inflammatory Efficacy.

Noncoding RNA. 2022-10-21

[10]
Contaminating transfection complexes can masquerade as small extracellular vesicles and impair their delivery of RNA.

J Extracell Vesicles. 2022-10

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