Rapid Degradation and High Renal Clearance of Cu₃BiS₃ Nanodots for Efficient Cancer Diagnosis and Photothermal Therapy <i>in Vivo</i>

A key challenge for the use of inorganic nanomedicines in clinical applications is their long-term accumulation in internal organs, which raises the common concern of the risk of adverse effects and inflammatory responses. It is thus necessary to rationally design inorganic nanomaterials with proper accumulation and clearance mechanism <i>in vivo</i>. Herein, we prepared ultrasmall Cu₃BiS₃ nanodots (NDs) as a single-phased ternary bimetal sulfide for photothermal cancer therapy guided by multispectral optoacoustic tomography (MSOT) and X-ray computed tomography (CT) due to bismuth’s excellent X-ray attenuation coefficient. We then monitored and investigated their absorption, distribution, metabolism, and excretion. We also used CT imaging to demonstrate that Cu₃BiS₃ NDs can be quickly removed through renal clearance, which may be related to their small size, rapid chemical transformation, and degradation in an acidic lysosomal environment as characterized by synchrotron radiation-based X-ray absorption near-edge structure spectroscopy. These results reveal that Cu₃BiS₃ NDs act as a simple but powerful “theranostic” nanoplatform for MSOT/CT imaging-guided tumor ablation with excellent metabolism and rapid clearance that will improve safety for clinical applications in the future