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早期神经祖细胞衍生的细胞外囊泡靶向递送至神经母细胞瘤细胞的特性研究视角

A Perspective on the Characterization of Early Neural Progenitor Cell-Derived Extracellular Vesicles for Targeted Delivery to Neuroblastoma Cells.

作者信息

Kırbaş Oğuz Kaan, Bozkurt Batuhan Turhan, Yıldırım Melis Rahime, Taşlı Pakize Neslihan, Abdik Hüseyin, Şahin Fikrettin, Avşar Abdik Ezgi

机构信息

Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, 34755, Turkey.

Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, İstanbul Sabahattin Zaim University, Istanbul, 34303, Turkey.

出版信息

Neurochem Res. 2024 Sep;49(9):2364-2378. doi: 10.1007/s11064-024-04165-1. Epub 2024 Jun 5.

DOI:10.1007/s11064-024-04165-1
PMID:38837091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310242/
Abstract

As an element of the cellular signaling systems, extracellular vesicles (EVs) exhibit many desirable traits for usage as targeted delivery vehicles. When administered, EVs cause little to no toxic or immune response, stay in circulation for longer periods compared to synthetic carriers, preferentially accumulate in tissues that are the same or similar to their cell-of-origin and can pass through the blood-brain barrier. Combined, these traits make neural EVs a particularly promising tool for delivering drugs to the brain. This study aims to combine tissue and EVs engineering to prepare neural differentiated cells derived EVs that exhibit neural properties, to develop an effective, tissue-homing drug and gene delivery platform for the brain. Early neural differentiated cell-derived EVs were produced with neural characteristics from neural differentiated human neonatal dermal fibroblasts. The EVs carried key neural proteins such as Nestin, Sox2 and Doublecortin. The cellular uptake of early neural differentiated cell-derived EVs was higher compared to non-neural EVs during in vitro uptake assays on neuroblastoma cells. Moreover, eND-EVs were significantly decreased the viability of neuroblastoma cells. In conclusion, this study revealed that early neural differentiated cell-derived EVs have potential as a promising drug carrier for the treatment of various neural disorders.

摘要

作为细胞信号系统的一个组成部分，细胞外囊泡（EVs）展现出许多作为靶向递送载体使用的理想特性。给药时，EVs几乎不会引起毒性或免疫反应，与合成载体相比，能在循环中停留更长时间，优先积聚在与其起源细胞相同或相似的组织中，并且可以穿过血脑屏障。综合这些特性，神经EVs成为向大脑递送药物的特别有前景的工具。本研究旨在结合组织和EVs工程技术，制备具有神经特性的神经分化细胞衍生的EVs，开发一种用于大脑的有效、组织归巢的药物和基因递送平台。早期神经分化细胞衍生的EVs由神经分化的人新生儿真皮成纤维细胞产生，并具有神经特征。这些EVs携带关键神经蛋白，如巢蛋白（Nestin）、性别决定区Y框蛋白2（Sox2）和双皮质素（Doublecortin）。在对神经母细胞瘤细胞的体外摄取试验中，早期神经分化细胞衍生的EVs的细胞摄取量高于非神经EVs。此外，早期神经分化细胞衍生的EVs显著降低了神经母细胞瘤细胞的活力。总之，本研究表明早期神经分化细胞衍生的EVs有潜力成为治疗各种神经疾病的有前景的药物载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/d22501f2097d/11064_2024_4165_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/2a3836a0f8c3/11064_2024_4165_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/1afe2e7e9341/11064_2024_4165_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/d3a34c86c04c/11064_2024_4165_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/eb2a86a40642/11064_2024_4165_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/4c889bba5627/11064_2024_4165_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/d22501f2097d/11064_2024_4165_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/2a3836a0f8c3/11064_2024_4165_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/1afe2e7e9341/11064_2024_4165_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/d3a34c86c04c/11064_2024_4165_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/eb2a86a40642/11064_2024_4165_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/4c889bba5627/11064_2024_4165_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949c/11310242/d22501f2097d/11064_2024_4165_Fig6_HTML.jpg

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