{"title":"Layered Double Hydroxides for Radium-223 Targeted Alpha Therapy with Elicitation of the Immune Response.","authors":"Mengdie Yang, Jianguo Li, Zongtai Han, Xiaohui Luan, Xiaoyi Zhang, Jie Gao, Shanshan Qin, Fei Yu","doi":"10.1002/adhm.202403175","DOIUrl":null,"url":null,"abstract":"<p><p>Targeted Alpha therapy (TAT) has promising application prospects in tumor therapy. It is very appealing to design alpha-emitting radiopharmaceuticals that can modulate the immune microenvironment to overcome the limitations of immunotherapy. Herein, Mg/Al layered double hydroxide nanomaterials (LDH) are utilized to load the alpha-emitting nuclide Radium-223 (<sup>223</sup>Ra), achieving precise delivery of <sup>223</sup>Ra to the tumor microenvironment. Dual-modal imaging is employed to dynamically monitor the in vivo distribution of <sup>223</sup>Ra-LDH, ensuring its prolonged retention at the tumor site. In vitro experimentsshowed that ionizing radiation from alpha-emitting nuclides effectively reduced glutathione (GSH) and produced large amounts of reactive oxygen species (ROS), which damaged mitochondria and released free calcium (Ca<sup>2+</sup>), thereby aggravating tumor cell death. Additionally, DNA double-strand breaks induced by alpha-emitting radiation triggered the STING signaling pathway, which in turn effectively induced immunogenic cell death (ICD) and promoted immune cell maturation and activation. The synergistic effect with immunotherapy triggered a powerful systemic antitumor immune response. Overall, this study develops a novel TAT therapeutic strategy with sufficient antitumor immunity.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2403175"},"PeriodicalIF":10.0000,"publicationDate":"2024-12-01","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.202403175","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
Targeted Alpha therapy (TAT) has promising application prospects in tumor therapy. It is very appealing to design alpha-emitting radiopharmaceuticals that can modulate the immune microenvironment to overcome the limitations of immunotherapy. Herein, Mg/Al layered double hydroxide nanomaterials (LDH) are utilized to load the alpha-emitting nuclide Radium-223 (223Ra), achieving precise delivery of 223Ra to the tumor microenvironment. Dual-modal imaging is employed to dynamically monitor the in vivo distribution of 223Ra-LDH, ensuring its prolonged retention at the tumor site. In vitro experimentsshowed that ionizing radiation from alpha-emitting nuclides effectively reduced glutathione (GSH) and produced large amounts of reactive oxygen species (ROS), which damaged mitochondria and released free calcium (Ca2+), thereby aggravating tumor cell death. Additionally, DNA double-strand breaks induced by alpha-emitting radiation triggered the STING signaling pathway, which in turn effectively induced immunogenic cell death (ICD) and promoted immune cell maturation and activation. The synergistic effect with immunotherapy triggered a powerful systemic antitumor immune response. Overall, this study develops a novel TAT therapeutic strategy with sufficient antitumor immunity.
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.