Metal-organic framework-based radiosensitizer for cancer therapy

Cancer persists as a leading global cause of mortality, highlighting the urgent need for more effective treatment strategies. Radiotherapy is a widely applied cancer treatment strategy in the clinic due to its ability to penetrate deep tissues and precisely target tumors. However, its effectiveness is often compromised by tumor radioresistance driven by hypoxia or rapid cell proliferation. In recent years, there has been a growing interest in developing radiosensitizers to improve the sensitivity of tumors to radiation. Advancements in nanomaterials and nanobiotechnology have accelerated progress in this area. In particular, metal-organic frameworks (MOFs)—which consist of high atomic number (high-Z) metal ions and organic linkers—demonstrate exceptional promise in enhancing tumor radiosensitivity. Their tunable composition, structural regularity, controllable porosity, facile functionalization, and high biocompatibility establish them as ideal radiosensitizing materials. Remarkably, MOFs have advanced to clinical trials as promising radiosensitizers. This review provides a comprehensive overview of recent advancements in MOFs as radiosensitizing agents and examines their potential applications in overcoming radioresistance and enhancing therapeutic outcomes. The aim is to improve researchers' understanding of the benefits and effectiveness of MOFs in radiation sensitization, inspire improvements in existing treatment methods, and encourage the exploration of new radiosensitization strategies. • Recent advances in metal-organic frameworks (MOFs) for radiotherapy are reviewed. • The structure, composition, and therapeutic mechanism of MOF-based radiosensitizers are summarized. • The applications of MOFs in radio-radiodynamic therapy, chemo-radiotherapy, and radioimmunotherapy are discussed. • Future directions for advancing radiotherapy applications and clinical translation of MOFs are proposed.