Renally Excretable Molybdenum Disulfide Nanoparticles as Contrast Agents for Dual-Energy Mammography and Computed Tomography

Compared with conventional mammography, contrast-enhanced dual-energy mammography (DEM) can improve tumor detection for people with dense breasts. However, currently available iodine-based contrast agents have several drawbacks such as their contraindication for use with renal insufficiency, high-dose requirement, and suboptimal contrast production. Molybdenum disulfide nanoparticles (MoS₂ NPs) have been shown to attenuate X-rays due to molybdenum’s relatively high atomic number while having good biocompatibility. However, work exploring their use as X-ray contrast agents has been limited. In this study, we have developed a novel aqueous synthesis yielding ultrasmall, 2 nm MoS₂ NPs with various small molecule coatings, including glutathione (GSH), penicillamine, and 2-mercaptopropionic acid (2MPA). These nanoparticles were shown to have low in vitro cytotoxicity when tested with various cell lines at concentrations up to 1 mg/mL. For the first time, these particles were shown to generate clinically relevant contrast in DEM. In DEM, MoS₂ NPs generated higher contrast than iopamidol, a commercially available X-ray contrast agent, while also generating substantial contrast in CT. Moreover, MoS₂ NPs demonstrated rapid elimination in vivo, mitigating long-term toxicity concerns. Together, the results presented here suggest the potential utility of MoS₂ NPs as a dual-modality X-ray contrast agent for DEM and CT.