Preclinical Evaluation of the GRPR-Targeting Antagonist RM26 Conjugated to the Albumin-Binding Domain for GRPR-Targeting Therapy of Cancer
| Parent link: | Pharmaceutics Vol. 12, iss. 10.— 2020.— [977, 17 p.] |
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| Korporativní autor: | |
| Další autoři: | , , , , , , , , , |
| Shrnutí: | Title screen The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections of peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation of the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) to an ABD (albumin-binding domain), we aimed to extend the blood circulation of peptides. The synthesized conjugate DOTA-ABD-RM26 was labelled with indium-111 and evaluated in vitro and in vivo. The labelled conjugate was stable in PBS and retained specificity and its antagonistic function against GRPR. The half-maximal inhibitory concentration (IC50) of natIn-DOTA-ABD-RM26 in the presence of human serum albumin was 49 ± 5 nM. [111In]In-DOTA-ABD-RM26 had a significantly longer residence time in blood and in tumors (without a significant decrease of up to 144 h pi) than the parental RM26 peptide. We conclude that the ABD-RM26 conjugate can be used for GRPR-targeted therapy and delivery of cytotoxic drugs. However, the undesirable elevated activity uptake in kidneys abolishes its use for radionuclide therapy. This proof-of-principle study justified further optimization of the molecular design of the ABD-RM26 conjugate. |
| Jazyk: | angličtina |
| Vydáno: |
2020
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| Témata: | |
| On-line přístup: | https://doi.org/10.3390/pharmaceutics12100977 |
| Médium: | Elektronický zdroj Kapitola |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=665199 |
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| 200 | 1 | |a Preclinical Evaluation of the GRPR-Targeting Antagonist RM26 Conjugated to the Albumin-Binding Domain for GRPR-Targeting Therapy of Cancer |f A. Abouzayed, Kh. Tano, A. Nagy [et al.] | |
| 203 | |a Text |c electronic | ||
| 300 | |a Title screen | ||
| 320 | |a [References: 42 tit.] | ||
| 330 | |a The targeting of gastrin-releasing peptide receptors (GRPR) was recently proposed for targeted therapy, e.g., radiotherapy. Multiple and frequent injections of peptide-based therapeutic agents would be required due to rapid blood clearance. By conjugation of the GRPR antagonist RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2) to an ABD (albumin-binding domain), we aimed to extend the blood circulation of peptides. The synthesized conjugate DOTA-ABD-RM26 was labelled with indium-111 and evaluated in vitro and in vivo. The labelled conjugate was stable in PBS and retained specificity and its antagonistic function against GRPR. The half-maximal inhibitory concentration (IC50) of natIn-DOTA-ABD-RM26 in the presence of human serum albumin was 49 ± 5 nM. [111In]In-DOTA-ABD-RM26 had a significantly longer residence time in blood and in tumors (without a significant decrease of up to 144 h pi) than the parental RM26 peptide. We conclude that the ABD-RM26 conjugate can be used for GRPR-targeted therapy and delivery of cytotoxic drugs. However, the undesirable elevated activity uptake in kidneys abolishes its use for radionuclide therapy. This proof-of-principle study justified further optimization of the molecular design of the ABD-RM26 conjugate. | ||
| 461 | |t Pharmaceutics | ||
| 463 | |t Vol. 12, iss. 10 |v [977, 17 p.] |d 2020 | ||
| 610 | 1 | |a электронный ресурс | |
| 610 | 1 | |a труды учёных ТПУ | |
| 610 | 1 | |a prostate cancer | |
| 610 | 1 | |a gastrin-releasing peptide receptor | |
| 610 | 1 | |a RM26 | |
| 610 | 1 | |a albumin-binding domain | |
| 610 | 1 | |a targeted therapy | |
| 610 | 1 | |a gastrin-releasing peptide receptors (GRPR) antagonist | |
| 610 | 1 | |a рецепторы | |
| 610 | 1 | |a рак | |
| 610 | 1 | |a пептиды | |
| 610 | 1 | |a терапия | |
| 610 | 1 | |a доклиническая оценка | |
| 701 | 1 | |a Abouzayed |b A. |g Ayman | |
| 701 | 1 | |a Tano |b Kh. |g Khanna | |
| 701 | 1 | |a Nagy |b A. |g Abel | |
| 701 | 1 | |a Rinne |b S. S. |g Sara | |
| 701 | 1 | |a Wadeea |b F. |g Fadya | |
| 701 | 1 | |a Kumar |b Sh. |g Sharmishtaa | |
| 701 | 1 | |a Westerlund |b K. |g Kristina | |
| 701 | 1 | |a Tolmachev |b V. M. |c specialist in the field of medical technology |c Director of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D |f 1961- |g Vladimir Maksimilianovich |3 (RuTPU)RU\TPU\pers\46552 |9 22210 | |
| 701 | 1 | |a Karlstrom |b A. E. |g Amelie Eriksson | |
| 701 | 1 | |a Orlova |b A. M. |c specialist in the field of medical technology |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D |f 1960- |g Anna Markovna |3 (RuTPU)RU\TPU\pers\46554 |9 22212 | |
| 712 | 0 | 2 | |a Национальный исследовательский Томский политехнический университет |b Исследовательская школа химических и биомедицинских технологий |b Научно-исследовательский центр "Онкотераностика" |3 (RuTPU)RU\TPU\col\27561 |
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