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Micron-sized radioactive microspheres or particles have gained widespread application in the localized treatment of various organ tumors, encompassing liver cancer, lung cancer, tongue cancer, pancreatic cancer, head and neck cancer, ovarian cancer, bone cancer, among others. As such, the design and development of novel multifunctional radioactive microspheres constitute a crucial foundation for achieving effective local treatment in liver cancer and other cancer types. This article critically reviews the current developmental landscape, identifies challenges, and explores opportunities in the field of radioactive internal irradiation microspheres in recent years. The insights provided serve as a valuable reference for selecting and determining the developmental direction of clinical brachytherapy treatment carriers.<\/jats:p>","DOI":"10.3389\/fbioe.2025.1621418","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T05:38:39Z","timestamp":1752644319000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Advancements in the investigation of radioactive microspheres for brachytherapy"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaohui","family":"Jiang","sequence":"first","affiliation":[{"name":"College of Physics and Electronic Engineering, Jining University","place":["Jining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Cancer Center, Dongguan Engineering Research Center for Innovative Boron Drugs and Novel Radioimmune Drugs, The 10th Affiliated Hospital of Southern Medical University, Southern Medical University","place":["Guangzhou, China"]},{"name":"Guangdong Engineering Research Center of Boron Neutron Therapy and Application in Malignant Tumors, The 10th Affiliated Hospital of Southern Medical University, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Cancer Center, Dongguan Engineering Research Center for Innovative Boron Drugs and Novel Radioimmune Drugs, The 10th Affiliated Hospital of Southern Medical University, Southern Medical University","place":["Guangzhou, China"]},{"name":"Guangdong Engineering Research Center of Boron Neutron Therapy and Application in Malignant Tumors, The 10th Affiliated Hospital of Southern Medical University, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3966","DOI":"10.3390\/molecules26133966","article-title":"Microspheres used in liver radioembolization: from conception to clinical effects","volume":"26","author":"Abadie","year":"2021","journal-title":"Molecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"257","DOI":"10.3390\/ph18020257","article-title":"Nano-radiopharmaceuticals in Colon cancer: current applications, challenges, and future directions","volume":"18","author":"Alkatheeri","year":"2025","journal-title":"Pharm. 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