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Lanthanide-based nanomaterials (Ln-NPs) offer versatile radiosensitizing theranostic potential to address these limitations. This review surveys Ln-NP-enabled radiotherapy from core physicochemical properties and synthesis to multi-level radiosensitization mechanisms, including high-Z dose amplification, reactive oxygen species generation, and DNA damage repair disruption. It also highlights MRI-contrast capability for image-guided dose painting therapy, benchmarks representative systems, and evaluates preclinical and clinical progress. 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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 School of Energy Power and Mechanical Engineering, North China Electric Power University, Beijing 102206, China; [shaofenghan@ncepu.edu.cn](shaofenghan@ncepu.edu.cn) (S.H.)  \n2 College of Science, Northeast Forestry University, Harbin 150040, China  \n3 College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China  \n* Correspondence: [cty@nefu.edu.cn](cty@nefu.edu.cn) (T.C.); [18935661020@nefu.edu.cn](18935661020@nefu.edu.cn) (S.G.-Z.)† These authors contributed equally to this work.  \nAbstract  \nRadiotherapy, a cornerstone of cancer treatment, is critically limited by tumor radioresistance and off-target toxicity. Lanthanide-based nanomaterials (Ln-NPs) have recently emerged as a versatile and promising class of theranostic radiosensitizers to overcome these hurdles. This review comprehensively outlines the state-of-the-art in Ln-NP-enabled radiotherapy, beginning with their fundamental physicochemical properties and synthesis and then delving into the multi-level mechanisms of radiosensitization, including high-Z element-mediated physical dose amplification, catalytic generation of reactive oxygen species (ROS), and disruption of DNA damage repair pathways. The unique capacity of certain Ln-NPs to serve as MRI contrast agents is highlighted as the foundation for imageguided, dose-painting radiotherapy. We critically summarize the preclinical and clinical progress of representative systems, benchmarking them against other high-Z nanomaterials. Finally, this work discusses the ongoing challenges, such as biocompatibility, targeted delivery, and regulatory hurdles, and envisages future directions, including combinatorial strategies with immunotherapy and the development of personalized nanotheranostic paradigms. Through this synthesis, this review aims to provide a clear roadmap for the continued development and clinical integration of lanthanide nanotheranostics in oncology.  \nKeywords: lanthanide nanomaterials; radiosensitizer; tumor radiotherapy; reactive oxygen species; review  \n1. Introduction  \nRadiotherapy is one of the cornerstones in the contemporary oncologic care, which can induce DNA breakage of tumor cells by high-energy rays, thus realizing the elimination of malignant tissues. However, the curative effect of traditional radiotherapy is often severely restricted by the inherent or acquired radiation resistance of tumor cells. At the same time, increasing the radiation dose to enhance the lethality will inevitably aggravate the damage of surrounding normal tissues. This fundamental contradiction between“dose-benefit” and “dose-toxicity” has seriously suppressed the promotion of therapeutic index. In order to break through this bottleneck, researchers put forward and extensively explored the strategy of radiosensitizer. Radiosensitizer is a kind of substance that can selectively improve the sensitivity of tumor tissue to radiation. Its core mechanism includes improving tumor hypoxia, inducing tumor cells to be in a more vulnerable cell cycle stage, inhibiting DNA damage repair pathway, and enhancing the deposition of radiation dose in tumor [1,2] . The selectivity of sensitizers can be divided into actively targeting  \ntumor-specific molecules or receptors, and “passively” relying on tumor-specific enhanced osmotic and retention effect (EPR) or low pH/hypoxia microenvironment. In addition, the introduction of nanotechnology, especially the design based on metal nanoparticles with hig","cbCaiqA0CSAnjewL","https://ap.wps.com/l/cbCaiqA0CSAnjewL","pdf",1256286,41,"English","# Introduction\n## Radiosensitizers and limits of traditional radiotherapy\n## Nanotechnology-based radiosensitizers and high-Z materials\n## Rationale for lanthanide nanomaterials in theranostic radiotherapy","[{\"question\":\"Why is radiotherapy limited in curing cancer despite its DNA-damaging effects?\",\"answer\":\"Traditional radiotherapy benefits are limited by inherent or acquired tumor radiation resistance. Increasing radiation dose can also worsen damage to surrounding normal tissues, reducing the therapeutic index.\"},{\"question\":\"What is the core mechanism of radiosensitizers in radiotherapy?\",\"answer\":\"Radiosensitizers improve tumor sensitivity by mechanisms such as enhancing hypoxia conditions, shifting tumor cells toward vulnerable cell cycle stages, inhibiting DNA damage repair pathways, and increasing radiation dose deposition in tumors.\"},{\"question\":\"How do lanthanide nanomaterials support theranostic radiotherapy?\",\"answer\":\"Lanthanide nanomaterials are considered promising due to high atomic number and rich electronic configurations, enabling strong interaction with radiation and functional integration for imaging and therapeutic roles. Some Ln-NPs can also act as MRI contrast agents to support image-guided dose painting radiotherapy.\"}]","Lanthanide Nanotheranostics in Radiotherapy - Review | PDF",1790763613,103]