通过将聚乙二醇连接到这些纳米转运体上,并可能释放到肿瘤中,从而增加模块化纳米转运体在小鼠肿瘤中的积累

IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yu. V. Khramtsov, A. V. Ulasov, T. A. Slastnikova,  G. P. Georgiev,  A. S. Sobolev
{"title":"通过将聚乙二醇连接到这些纳米转运体上,并可能释放到肿瘤中,从而增加模块化纳米转运体在小鼠肿瘤中的积累","authors":"Yu. V. Khramtsov,&nbsp;A. V. Ulasov,&nbsp;T. A. Slastnikova,&nbsp; G. P. Georgiev,&nbsp; A. S. Sobolev","doi":"10.1134/S1607672924601240","DOIUrl":null,"url":null,"abstract":"<p>Previously, polypeptide constructs—modular nanotransporters (MNTs)—were created to deliver biologically active molecules into the nuclei of melanoma cells. In the present work, polyethylene glycol (PEG) molecules were attached to them at the N-terminal cysteine, both with the possibility of their subsequent cleavage at the hydrolysis site of tumor-specific proteases, and without this site (non-detachable PEG). All MNT variants labeled with the radioisotope <sup>111</sup>In were administered to mice with inoculated Cloudman S91 melanoma. The kinetics of radioactivity distribution in the mouse body was studied using single-photon emission computed tomography. Analysis of the obtained data using a compartmental mathematical model allowed us to establish that the attachment of PEG to MNT increased its lifetime in the blood and significantly increased its accumulation in the tumor. Addition of a PEG detachment site by tumor-specific protease led to a strong retention of this MNT in the tumor. The data obtained can serve as a basis for the creation of new effective antitumor drugs.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"521 1","pages":"165 - 168"},"PeriodicalIF":0.8000,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Increasing the Accumulation of Modular Nanotransporters in Mouse Tumors by Attaching Polyethylene Glycol to These Nanotransporters with the Possibility of Its Release into the Tumors\",\"authors\":\"Yu. V. Khramtsov,&nbsp;A. V. Ulasov,&nbsp;T. A. Slastnikova,&nbsp; G. P. Georgiev,&nbsp; A. S. Sobolev\",\"doi\":\"10.1134/S1607672924601240\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Previously, polypeptide constructs—modular nanotransporters (MNTs)—were created to deliver biologically active molecules into the nuclei of melanoma cells. In the present work, polyethylene glycol (PEG) molecules were attached to them at the N-terminal cysteine, both with the possibility of their subsequent cleavage at the hydrolysis site of tumor-specific proteases, and without this site (non-detachable PEG). All MNT variants labeled with the radioisotope <sup>111</sup>In were administered to mice with inoculated Cloudman S91 melanoma. The kinetics of radioactivity distribution in the mouse body was studied using single-photon emission computed tomography. Analysis of the obtained data using a compartmental mathematical model allowed us to establish that the attachment of PEG to MNT increased its lifetime in the blood and significantly increased its accumulation in the tumor. Addition of a PEG detachment site by tumor-specific protease led to a strong retention of this MNT in the tumor. The data obtained can serve as a basis for the creation of new effective antitumor drugs.</p>\",\"PeriodicalId\":529,\"journal\":{\"name\":\"Doklady Biochemistry and Biophysics\",\"volume\":\"521 1\",\"pages\":\"165 - 168\"},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2025-04-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Doklady Biochemistry and Biophysics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1134/S1607672924601240\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Doklady Biochemistry and Biophysics","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1134/S1607672924601240","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

以前,多肽结构——模块化纳米转运体(mnt)——被用来将生物活性分子传递到黑色素瘤细胞的细胞核中。在本研究中,聚乙二醇(PEG)分子附着在它们的n端半胱氨酸上,两者都有可能在肿瘤特异性蛋白酶的水解位点上进行随后的裂解,或者没有这个位点(不可分离的PEG)。所有标记有放射性同位素111In的MNT变体均被给予接种了Cloudman S91黑色素瘤的小鼠。采用单光子发射计算机断层扫描技术研究了放射性在小鼠体内的分布动力学。使用区室数学模型分析获得的数据使我们能够确定PEG与MNT的附着增加了其在血液中的寿命,并显着增加了其在肿瘤中的积累。通过肿瘤特异性蛋白酶添加PEG分离位点导致这种MNT在肿瘤中的强烈保留。所获得的数据可以作为创造新的有效的抗肿瘤药物的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Increasing the Accumulation of Modular Nanotransporters in Mouse Tumors by Attaching Polyethylene Glycol to These Nanotransporters with the Possibility of Its Release into the Tumors

Previously, polypeptide constructs—modular nanotransporters (MNTs)—were created to deliver biologically active molecules into the nuclei of melanoma cells. In the present work, polyethylene glycol (PEG) molecules were attached to them at the N-terminal cysteine, both with the possibility of their subsequent cleavage at the hydrolysis site of tumor-specific proteases, and without this site (non-detachable PEG). All MNT variants labeled with the radioisotope 111In were administered to mice with inoculated Cloudman S91 melanoma. The kinetics of radioactivity distribution in the mouse body was studied using single-photon emission computed tomography. Analysis of the obtained data using a compartmental mathematical model allowed us to establish that the attachment of PEG to MNT increased its lifetime in the blood and significantly increased its accumulation in the tumor. Addition of a PEG detachment site by tumor-specific protease led to a strong retention of this MNT in the tumor. The data obtained can serve as a basis for the creation of new effective antitumor drugs.

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
Doklady Biochemistry and Biophysics
Doklady Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
1.60
自引率
12.50%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.
×
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:481959085
Book学术官方微信