文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

利用脂质锚定物控制影响外源货物蛋白与细胞外囊泡结合的物理和生化参数,可实现高负载和有效的细胞内递送。

Control of Physical and Biochemical Parameters Influencing Exogeneous Cargo Protein Association to Extracellular Vesicles Using Lipid Anchors Enables High Loading and Effective Intracellular Delivery.

作者信息

Marquant Antonin, Berthelot Jade, Bich Claudia, Elfekih Zeineb Ibn, Simon Laurianne, Robin Baptiste, Chopineau Joël, Wang David Tianpei, Emerson Samuel Jay, Wang Aijun, Benedetti Clément, Langlois Simon, Guglielmi Laurence, Martineau Pierre, Aubert-Pouëssel Anne, Morille Marie

机构信息

ICGM Montpellier University, CNRS, ENSCM Montpellier France.

Institut des Biomolécules Max Mousseron (IBMM) Montpellier France.

出版信息

J Extracell Biol. 2025 May 14;4(5):e70048. doi: 10.1002/jex2.70048. eCollection 2025 May.


DOI:10.1002/jex2.70048
PMID:40371218
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12077271/
Abstract

Despite biomolecule delivery is a natural function of extracellular vesicles (EVs), low loading of exogenous macromolecules such as proteins into EVs limits their interest as convincing protein delivery systems for health applications. In this context, lipid-anchorage of exogenous cargo into EV membrane recently emerged as a promising option to enable their vectorisation into cells. Nevertheless, this option was not explored for protein intracellular delivery, and further characterisation of critical parameters governing the association of a lipid-anchored cargo protein to EVs is still needed to confirm the relevance of this anchorage strategy. Therefore, we sought to identify these parameters in a precise and quantitative manner, using bulk and single nanoparticle analysis methods to identify protein loading capacity and subsequent intracellular delivery. We identified incubation temperature, cargo concentration, lipid anchor (LA) structure (lipid nature, linker) and EV origin as critical factors influencing maximal EV loading capacity. Precise control of these parameters enabled to load cargo protein close to EV saturation without hindering cellular delivery. The structural properties of LA influenced not only cargo protein/EV association but also intracellular delivery into different carcinoma cell lines. By thoroughly characterising Lipid-PEG-protein anchorage, this study evidences the interest of this tunable and controllable approach for efficient EV protein delivery.

摘要

尽管生物分子递送是细胞外囊泡(EVs)的天然功能,但诸如蛋白质等外源性大分子在EVs中的低负载量限制了它们作为用于健康应用的可靠蛋白质递送系统的价值。在这种背景下,将外源性货物脂质锚定到EV膜上最近成为一种有前景的选择,以使其能够递送至细胞内。然而,这种方法尚未用于蛋白质的细胞内递送,并且仍需要进一步表征控制脂质锚定货物蛋白与EVs结合的关键参数,以确认这种锚定策略的相关性。因此,我们试图以精确和定量的方式确定这些参数,使用整体和单纳米颗粒分析方法来确定蛋白质负载能力和随后的细胞内递送。我们确定孵育温度、货物浓度、脂质锚(LA)结构(脂质性质、连接子)和EV来源是影响最大EV负载能力的关键因素。对这些参数的精确控制能够在不阻碍细胞递送的情况下将货物蛋白负载至接近EV饱和状态。LA的结构特性不仅影响货物蛋白/EV的结合,还影响其向不同癌细胞系的细胞内递送。通过全面表征脂质-聚乙二醇-蛋白锚定,本研究证明了这种可调节和可控方法对于高效EV蛋白递送的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/456842c00da5/JEX2-4-e70048-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/074c84720241/JEX2-4-e70048-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/221e8a1f004b/JEX2-4-e70048-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/87aeba98a214/JEX2-4-e70048-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/932dd78442fa/JEX2-4-e70048-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/75542417271d/JEX2-4-e70048-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/22dbca2007a8/JEX2-4-e70048-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/2a7503a48e35/JEX2-4-e70048-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/456842c00da5/JEX2-4-e70048-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/074c84720241/JEX2-4-e70048-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/221e8a1f004b/JEX2-4-e70048-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/87aeba98a214/JEX2-4-e70048-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/932dd78442fa/JEX2-4-e70048-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/75542417271d/JEX2-4-e70048-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/22dbca2007a8/JEX2-4-e70048-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/2a7503a48e35/JEX2-4-e70048-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/12077271/456842c00da5/JEX2-4-e70048-g002.jpg

相似文献

[1]
Control of Physical and Biochemical Parameters Influencing Exogeneous Cargo Protein Association to Extracellular Vesicles Using Lipid Anchors Enables High Loading and Effective Intracellular Delivery.

J Extracell Biol. 2025-5-14

[2]
A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery.

J Extracell Vesicles. 2016-5-13

[3]
Virus-Free Method to Control and Enhance Extracellular Vesicle Cargo Loading and Delivery.

ACS Appl Bio Mater. 2023-3-20

[4]
Quantification of protein cargo loading into engineered extracellular vesicles at single-vesicle and single-molecule resolution.

J Extracell Vesicles. 2021-8

[5]
Breaking free: endocytosis and endosomal escape of extracellular vesicles.

Extracell Vesicles Circ Nucl Acids. 2023-6-30

[6]
The lipid-binding D4 domain of perfringolysin O facilitates the active loading of exogenous cargo into extracellular vesicles.

FEBS Lett. 2024-2

[7]
Current Strategies for Exosome Cargo Loading and Targeting Delivery.

Cells. 2023-5-17

[8]
TOP-EVs: Technology of Protein delivery through Extracellular Vesicles is a versatile platform for intracellular protein delivery.

J Control Release. 2023-3

[9]
Chinese hamster ovary cell line engineering strategies for modular production of custom extracellular vesicles.

Biotechnol Bioeng. 2024-9

[10]
Endocytosis of Extracellular Vesicles and Release of Their Cargo from Endosomes.

ACS Nano. 2020-4-28

引用本文的文献

[1]
Temporal and Severity-Dependent Alterations in Plasma Extracellular Vesicle Profiles Following Spinal Cord Injury.

Cells. 2025-7-11

本文引用的文献

[1]
HaloTag display enables quantitative single-particle characterisation and functionalisation of engineered extracellular vesicles.

J Extracell Vesicles. 2024-7

[2]
Compartmentalized drug localization studies in extracellular vesicles for anticancer therapy.

Nanoscale Adv. 2023-11-8

[3]
Creating Designer Engineered Extracellular Vesicles for Diverse Ligand Display, Target Recognition, and Controlled Protein Loading and Delivery.

Adv Sci (Weinh). 2023-12

[4]
The cellular response to extracellular vesicles is dependent on their cell source and dose.

Sci Adv. 2023-9

[5]
Quantitative and functional characterisation of extracellular vesicles after passive loading with hydrophobic or cholesterol-tagged small molecules.

J Control Release. 2023-9

[6]
Engineering protein-based therapeutics through structural and chemical design.

Nat Commun. 2023-4-27

[7]
Surface display of functional moieties on extracellular vesicles using lipid anchors.

J Control Release. 2023-5

[8]
TOP-EVs: Technology of Protein delivery through Extracellular Vesicles is a versatile platform for intracellular protein delivery.

J Control Release. 2023-3

[9]
Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine.

Nat Biomed Eng. 2022-7

[10]
Discovery of an Oral, Rule of 5 Compliant, Interleukin 17A Protein-Protein Interaction Modulator for the Potential Treatment of Psoriasis and Other Inflammatory Diseases.

J Med Chem. 2022-7-14

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索