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, A. V. Ulasov, T. A. Slastnikova, G. P. Georgiev, 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, A. V. Ulasov, T. A. Slastnikova, G. P. Georgiev, 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}
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.
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.