Precision Chemoradiotherapy via EGFR Targeting with Radiotherapy-Activated Drug Conjugates.
Uložené v:
| Názov: | Precision Chemoradiotherapy via EGFR Targeting with Radiotherapy-Activated Drug Conjugates. |
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| Autori: | Lin S; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 Guangdong, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Luo J; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 Guangdong, China., Yang J; PolyAdvant, Shenzhen, 518055 Guangdong, China., Tan K; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 Guangdong, China., Xing Q; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 Guangdong, China., Zhang S; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 Guangdong, China., Gao Q; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 Guangdong, China., Geng J; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 Guangdong, China. |
| Zdroj: | Journal of medicinal chemistry [J Med Chem] 2025 Nov 13; Vol. 68 (21), pp. 22769-22778. Date of Electronic Publication: 2025 Oct 23. |
| Spôsob vydávania: | Journal Article |
| Jazyk: | English |
| Informácie o časopise: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| Výrazy zo slovníka MeSH: | ErbB Receptors*/metabolism , ErbB Receptors*/antagonists & inhibitors , Chemoradiotherapy* , Immunoconjugates*/pharmacology , Immunoconjugates*/chemistry , Immunoconjugates*/therapeutic use , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry , Antineoplastic Agents*/therapeutic use, Animals ; Humans ; Mice ; Cell Line, Tumor ; Azo Compounds/chemistry ; Azo Compounds/pharmacology ; Mice, Nude ; Female ; Mice, Inbred BALB C ; Xenograft Model Antitumor Assays |
| Abstrakt: | The strategy of concurrent chemoradiotherapy (CCRT) has been developed, aiming to leverage the benefits of chemotherapy and radiotherapy while mitigating their respective limitations. In this study, we innovatively employed an azobenzene structure as a pivotal group responsive to X-ray irradiation, designing radiotherapy-triggered azobenzene linkers, augmented with an antibody as a targeting moiety, to formulate radiotherapy-triggered antibody-drug conjugates (RT-ADCs). These conjugates can precisely target those tumor cells with high expression of the epidermal growth factor receptor (EGFR), thereby accumulating at the tumor site. Upon exposure to X-ray irradiation, the azobenzene linkers undergo cleavage, resulting in the localized release of cytotoxic agents at the tumor site, effectively eliminating tumor cells. In vivo assays demonstrate that the tumors in the treatment group of mice nearly vanished, with tumor growth inhibition (TGI) exceeding 90%, and median survival time (MST) significantly extended. We are confident that RT-ADC holds substantial clinical application potential and can profoundly influence the field of deep-seated tumor therapy. |
| Substance Nomenclature: | EC 2.7.10.1 (ErbB Receptors) 0 (Immunoconjugates) EC 2.7.10.1 (EGFR protein, human) 0 (Antineoplastic Agents) 0 (Azo Compounds) F0U1H6UG5C (azobenzene) |
| Entry Date(s): | Date Created: 20251023 Date Completed: 20251113 Latest Revision: 20251113 |
| Update Code: | 20251114 |
| DOI: | 10.1021/acs.jmedchem.5c01716 |
| PMID: | 41129299 |
| Databáza: | MEDLINE |
Nájsť tento článok vo Web of Science | Abstrakt: | The strategy of concurrent chemoradiotherapy (CCRT) has been developed, aiming to leverage the benefits of chemotherapy and radiotherapy while mitigating their respective limitations. In this study, we innovatively employed an azobenzene structure as a pivotal group responsive to X-ray irradiation, designing radiotherapy-triggered azobenzene linkers, augmented with an antibody as a targeting moiety, to formulate radiotherapy-triggered antibody-drug conjugates (RT-ADCs). These conjugates can precisely target those tumor cells with high expression of the epidermal growth factor receptor (EGFR), thereby accumulating at the tumor site. Upon exposure to X-ray irradiation, the azobenzene linkers undergo cleavage, resulting in the localized release of cytotoxic agents at the tumor site, effectively eliminating tumor cells. In vivo assays demonstrate that the tumors in the treatment group of mice nearly vanished, with tumor growth inhibition (TGI) exceeding 90%, and median survival time (MST) significantly extended. We are confident that RT-ADC holds substantial clinical application potential and can profoundly influence the field of deep-seated tumor therapy. |
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| ISSN: | 1520-4804 |
| DOI: | 10.1021/acs.jmedchem.5c01716 |