Abstract
Radiotherapy, 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 image-guided, 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.