Smart responsive-calcium carbonate nanoparticles for dual-model cancer imaging and treatment

Contrast-enhanced ultrasound (CEUS) is widely applied in cancer diagnosis clinically. However, the gas-filled contrast agents are unstable in the blood and exhibit shorter imaging time, which limit their clinical use. In this study, a diagnostic nanoparticle system was developed for dual-mode imaging (ultrasound and fluorescence), which after encapsulation with doxorubicin (DOX) demonstrated simultaneous therapeutic function towards cancer treatment. Thus, calcium carbonate (CaCO₃) nanoparticles were encapsulated with doxorubicin (DOX) to obtain CaCO₃-DOX. Under acidic conditions, it produced carbon dioxide (CO₂) to enhance ultrasound imaging and increase the release of DOX. After intravenously injecting CaCO₃-DOX to tumor-bearing mice, in the presence of an ultrasound field, CO₂bubbles were sufficiently generated at the tumor tissues for echogenic reflectivity. Also, the indocyanine green (ICG) was encapsulated into CaCO₃ nanoparticles, to further detect the tumor with fluorescence. The resultant theranostic nanoparticle system exhibited therapeutic efficacy towards tumour-bearing mice. Overall, this investigation provides an attractive strategy for dual-mode cancer diagnostics.