ttmt1修饰的细胞外小泡靶向间变性甲状腺癌BRAF突变,通过CRISPR/Cas9递送逆转Vemurafenib耐药

IF 14.5 1区 医学 Q1 CELL BIOLOGY
Shuo Zhang, Zhenrong Ji, Xiaoyu Cheng, Yue Ma, Mingliang Feng, Dasheng Cai, Tao Bai
{"title":"ttmt1修饰的细胞外小泡靶向间变性甲状腺癌BRAF突变,通过CRISPR/Cas9递送逆转Vemurafenib耐药","authors":"Shuo Zhang,&nbsp;Zhenrong Ji,&nbsp;Xiaoyu Cheng,&nbsp;Yue Ma,&nbsp;Mingliang Feng,&nbsp;Dasheng Cai,&nbsp;Tao Bai","doi":"10.1002/jev2.70170","DOIUrl":null,"url":null,"abstract":"<p>This study investigates a novel approach to overcome Vemurafenib resistance in BRAF-mutant Anaplastic thyroid carcinoma (ATC) using CRISPR/Cas9 gene editing and TMTP1-modified extracellular vesicles (TMTP1-sgBRAF-EVs). By knocking out the BRAF gene, the study elucidates Vemurafenib-induced ferroptosis mechanisms involving lipid peroxidation and reactive oxygen species (ROS) generation in ATC cells. The developed TMTP1-sgBRAF-EVs system demonstrates superior tumour-targeting and drug delivery capabilities, significantly enhancing Vemurafenib efficacy in both in vitro and in vivo models. This innovative combination of gene editing technology with a nanoparticle delivery system shows promising potential as a therapeutic strategy for treating aggressive BRAF-mutant ATC.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"14 9","pages":""},"PeriodicalIF":14.5000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70170","citationCount":"0","resultStr":"{\"title\":\"TMTP1-Modified Small Extracellular Vesicles Target BRAF Mutation in Anaplastic Thyroid Cancer Reversing Vemurafenib Resistance With CRISPR/Cas9 Delivery\",\"authors\":\"Shuo Zhang,&nbsp;Zhenrong Ji,&nbsp;Xiaoyu Cheng,&nbsp;Yue Ma,&nbsp;Mingliang Feng,&nbsp;Dasheng Cai,&nbsp;Tao Bai\",\"doi\":\"10.1002/jev2.70170\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>This study investigates a novel approach to overcome Vemurafenib resistance in BRAF-mutant Anaplastic thyroid carcinoma (ATC) using CRISPR/Cas9 gene editing and TMTP1-modified extracellular vesicles (TMTP1-sgBRAF-EVs). By knocking out the BRAF gene, the study elucidates Vemurafenib-induced ferroptosis mechanisms involving lipid peroxidation and reactive oxygen species (ROS) generation in ATC cells. The developed TMTP1-sgBRAF-EVs system demonstrates superior tumour-targeting and drug delivery capabilities, significantly enhancing Vemurafenib efficacy in both in vitro and in vivo models. This innovative combination of gene editing technology with a nanoparticle delivery system shows promising potential as a therapeutic strategy for treating aggressive BRAF-mutant ATC.</p>\",\"PeriodicalId\":15811,\"journal\":{\"name\":\"Journal of Extracellular Vesicles\",\"volume\":\"14 9\",\"pages\":\"\"},\"PeriodicalIF\":14.5000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://isevjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70170\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Extracellular Vesicles\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.70170\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Extracellular Vesicles","FirstCategoryId":"3","ListUrlMain":"https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.70170","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

本研究探讨了一种利用CRISPR/Cas9基因编辑和tmtp1修饰的细胞外囊泡(tmtp1 - sgbraf - ev)克服braf突变的间变性甲状腺癌(ATC)中Vemurafenib耐药的新方法。通过敲除BRAF基因,该研究阐明了vemurafenib诱导的ATC细胞中涉及脂质过氧化和活性氧(ROS)产生的铁死亡机制。开发的tmtp1 - sgbraf - ev系统显示出卓越的肿瘤靶向和药物递送能力,在体外和体内模型中显著提高Vemurafenib的疗效。这种基因编辑技术与纳米颗粒递送系统的创新组合显示出治疗侵袭性braf突变ATC的治疗策略的巨大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

TMTP1-Modified Small Extracellular Vesicles Target BRAF Mutation in Anaplastic Thyroid Cancer Reversing Vemurafenib Resistance With CRISPR/Cas9 Delivery

TMTP1-Modified Small Extracellular Vesicles Target BRAF Mutation in Anaplastic Thyroid Cancer Reversing Vemurafenib Resistance With CRISPR/Cas9 Delivery

This study investigates a novel approach to overcome Vemurafenib resistance in BRAF-mutant Anaplastic thyroid carcinoma (ATC) using CRISPR/Cas9 gene editing and TMTP1-modified extracellular vesicles (TMTP1-sgBRAF-EVs). By knocking out the BRAF gene, the study elucidates Vemurafenib-induced ferroptosis mechanisms involving lipid peroxidation and reactive oxygen species (ROS) generation in ATC cells. The developed TMTP1-sgBRAF-EVs system demonstrates superior tumour-targeting and drug delivery capabilities, significantly enhancing Vemurafenib efficacy in both in vitro and in vivo models. This innovative combination of gene editing technology with a nanoparticle delivery system shows promising potential as a therapeutic strategy for treating aggressive BRAF-mutant ATC.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信