Yun Gao, Xiaotong Wang, Can Chen, Lei Chen, Xiaoyi Cao, Mengyao Wu, Yi Zhou, Jianfeng Zeng, Mingyuan Gao
{"title":"In Vivo Bioorthogonal Radiolabeling of Nanoparticles to Minimize Liver Radiation.","authors":"Yun Gao, Xiaotong Wang, Can Chen, Lei Chen, Xiaoyi Cao, Mengyao Wu, Yi Zhou, Jianfeng Zeng, Mingyuan Gao","doi":"10.1002/adhm.202503438","DOIUrl":null,"url":null,"abstract":"<p><p>Radiolabeled nanoparticles hold great promise in precision medicine due to its versatile applications in disease imaging and therapy. However, its clinical translation is often hindered by excessive accumulation in reticuloendothelial system organs, particularly the liver, which can lead to radiation-induced toxicity. Herein, an in vivo selective radiolabeling strategy is reported that exploits the distinct subcellular fates of nanoparticles in tumors versus liver. A biorthogonal nanosystem composed of trans-cyclooctene (TCO)-functionalized iron oxide nanoparticles (Fe<sub>3</sub>O<sub>4</sub>@TCO) and a radiolabeled tetrazine probe (<sup>177</sup>Lu-DOTA-Tz) is constructed to validate this concept. Owing to the hydrophilic nature, <sup>177</sup>Lu-DOTA-Tz cannot penetrate cell membranes, resulting in spatially restricted bioorthogonal labeling in the extracellular space. At tumor sites, Fe<sub>3</sub>O<sub>4</sub>@TCO nanoparticles accumulate via the enhanced permeability and retention effect and remain accessible for efficient binding with <sup>177</sup>Lu-DOTA-Tz. In contrast, in the liver, nanoparticles are predominantly internalized by liver cells, and its intracellular localization prevents interaction with the probe, thereby minimizing hepatic radiation retention. By harnessing these subcellular distribution differences, the approach achieves selective in vivo radiolabeling and significantly improves the tumor-to-liver radiation ratio. This study provides a biologically informed strategy for designing radiolabeled nanoplatforms with enhanced safety profiles for theranostic applications.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03438"},"PeriodicalIF":9.6000,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Healthcare Materials","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1002/adhm.202503438","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Radiolabeled nanoparticles hold great promise in precision medicine due to its versatile applications in disease imaging and therapy. However, its clinical translation is often hindered by excessive accumulation in reticuloendothelial system organs, particularly the liver, which can lead to radiation-induced toxicity. Herein, an in vivo selective radiolabeling strategy is reported that exploits the distinct subcellular fates of nanoparticles in tumors versus liver. A biorthogonal nanosystem composed of trans-cyclooctene (TCO)-functionalized iron oxide nanoparticles (Fe3O4@TCO) and a radiolabeled tetrazine probe (177Lu-DOTA-Tz) is constructed to validate this concept. Owing to the hydrophilic nature, 177Lu-DOTA-Tz cannot penetrate cell membranes, resulting in spatially restricted bioorthogonal labeling in the extracellular space. At tumor sites, Fe3O4@TCO nanoparticles accumulate via the enhanced permeability and retention effect and remain accessible for efficient binding with 177Lu-DOTA-Tz. In contrast, in the liver, nanoparticles are predominantly internalized by liver cells, and its intracellular localization prevents interaction with the probe, thereby minimizing hepatic radiation retention. By harnessing these subcellular distribution differences, the approach achieves selective in vivo radiolabeling and significantly improves the tumor-to-liver radiation ratio. This study provides a biologically informed strategy for designing radiolabeled nanoplatforms with enhanced safety profiles for theranostic applications.
期刊介绍:
Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.