Advance of different strategies to achieve radiosensitivity based on nanomaterials

Radiotherapy (RT) stands as one of the most widely used and effective modalities in the clinical treatment of malignant tumors. A key advancement in modern precision RT technology is to improve therapeutic gain ratios through physical techniques. However, RT efficacy remains constrained by multiple factors, including the low sensitivity of tumor tissue to RT, the dose-limiting constraints of RT, and the intrinsic capacity of tumors to repair radiation-induced damage. Thus, enhancing the sensitivity of tumor cells to RT has become a current research focus. The sensitivity of malignant tumors to RT is governed primarily by multiple factors, including the intratumoral oxygen levels, specific redox states, distinct tumor cell cycle phases, and the inherent physiological barriers imposed by the tumor microenvironment (TME). In recent years, bionanomaterials have garnered substantial attention in biomedical research due to their unique physicochemical properties and functional versatility. Their application as radiosensitizers to augment tumor tissue responsiveness to RT has rapidly evolved into a prominent research frontier. In this review, we first elucidate the fundamentals of RT and bionanomaterials, followed by a comprehensive analysis of nanomaterial-based radiosensitization strategies tailored to address distinct influencing factors. We further outline emerging synergistic approaches that combine nanomaterials with RT to induce regulated tumor cell death (RCD) and summarize the relevant clinical research on the use of nanomaterials as radiosensitizers, aiming to highlight the research progress in nanomaterial-enabled RT enhancement. Finally, the challenges and opportunities for bionanomaterials as radiosensitizers are discussed further, providing actionable insights for translational research.