2025/10/23 by Shanmeng Lin, Jinyan Luo, Jinying Yang +6
Medicine · #HER2/EGFR in Cancer Research #Lung Cancer Treatments and Mutations #Medical Imaging Techniques and Applications
paper · doi:10.1021/acs.jmedchem.5c01716
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.