Human serum albumin-based KBiF(4)@HSA nanoclusters for dual-energy computed tomography and glutathione-scavenging radiotherapy of breast cancer.

BACKGROUND: Breast cancer remains the most common malignancy among women worldwide. While traditional computed tomography (CT) scans and image-guided radiotherapy are widely used for breast cancer diagnosis and treatment, their efficacy is often limited. METHODS AND RESULTS: In this study, we successfully synthesized human serum albumin (HSA)-based KBiF(4) nanoclusters through a simple one-pot biomimetic mineralization strategy. Compared to the clinical contrast agent iohexol, KBiF(4)@HSA significantly enhances dual-energy CT (DECT) imaging contrast at high keV levels, offering improved diagnostic accuracy for breast cancer. Furthermore, KBiF(4)@HSA exhibits a remarkable ability to scavenge elevated glutathione (GSH) levels and promote reactive oxygen species (ROS) generation. When combined with radiotherapy, KBiF(4)@HSA substantially increases X-ray dose deposition at tumor sites, leading to enhanced DNA damage and suppression of breast cancer progression. Importantly, KBiF(4)@HSA demonstrates excellent biocompatibility in vivo, with no significant tissue damage or inflammation observed. CONCLUSIONS: This study presents a novel approach for the development of biocompatible DECT contrast agents and radiosensitizers, offering a promising strategy to enhance breast cancer diagnosis and treatment. However, the efficacy of this approach needs to be further validated across diverse breast cancer subtypes to ensure its broad applicability, which emphasizes the necessity for continued research to fully translate this innovative technology into clinical practice.