ABSTRACT X‐ray‐based cancer therapies, including conventional radiotherapy (RT) and emerging radiodynamic therapy, are constrained by challenges such as insufficient tumor‐specific radiation absorption, collateral damage to healthy tissues, hypoxia‐induced resistance, and limited efficacy against metastatic tumors. Recent advances in nanomedicine offer versatile strategies to overcome these limitations. High atomic number (high‐Z) nanomaterials serve as radiosensitizers, enhancing x‐ray energy deposition at tumor sites while enabling precise imaging‐guided treatment. Importantly, x‐ray spectrometric techniques, including x‐ray fluorescence spectroscopy, x‐ray photoelectron spectroscopy, and x‐ray absorption spectroscopy, play a critical role in this field by enabling quantitative characterization of nanoparticle composition, surface chemistry, electronic structure, and in vivo biodistribution, supporting the optimization of energy‐dependent attenuation, dose enhancement, and nanoparticle–tissue interactions. Multifunctional nanocarriers facilitate combination therapies, integrating RT with chemotherapy, photodynamic therapy, photothermal therapy, and immunotherapy to induce synergistic anticancer effects. Modulating the tumor microenvironment through oxygen delivery, in situ oxygen generation, glutathione depletion, and peroxide decomposition amplifies ROS production, promoting DNA damage and inhibiting repair mechanisms. Radioprotective nanomaterials selectively shield normal tissues from oxidative damage, allowing the safe use of higher radiation doses. Radiodynamic therapy (RDT) employs x‐ray‐activated fluorescence to trigger photosensitizers or uses single‐component nanomaterials to generate ROS, offering deeper tissue penetration and lower radiation doses than conventional RT. Despite promising preclinical outcomes, clinical translation remains challenging due to nanomaterial biocompatibility, heterogeneous tumor distribution, photon energy dependence, and long‐term safety. Continued integration of x‐ray spectrometry with nanomaterial design, imaging‐guided therapy, and immunomodulatory approaches is expected to advance precision radiotherapy and improve clinical outcomes.
Alqinnah et al. (2026) studied this question.