Rare-earth scintillating materials have been widely utilized in nuclear image technique, security screening and high energy physics research. Researchers have devoted extensive efforts to size design, surface modification, and drug assembly to transform them into prospective nanomaterials for diagnostics and cancer treatment. This review endeavors to summarize the advanced preparation technology and design concept of rare-earth nanocrystalline scintillators (RENSs), and offers fundamental guidance for the application of various materials in biomedical research. Specifically, it focuses on RENSs with excellent biocompatibility, outstanding stability, uniform size distribution, and strong drug loading capacity to meet subsequent practical applications. Additionally, this review reports on the application of RENSs in the biomedical field. Specifically, bioimaging and antitumor therapy are the most prevalently utilized and promising areas. X-ray excited optical imaging (XEOL) is combined with advanced imaging techniques (CT, MRI, etc.) to obtain comprehensive information about deep tissue. The combination of X-ray radiation therapy and photodynamic therapy technology can realize safe anti-tumor therapy under the condition of low-dose irradiation. Furthermore, this review also enumerates several recent highlight research strategies and the prospects of RENSs in the biomedical application in the future.
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