pH-Controlled Gas-Generating Mineralized Nanoparticles: A Theranostic Agent for Ultrasound Imaging and Therapy of Cancers

We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO₃) hybrid nanoparticles (DOX-CaCO₃-MNPs) through a block copolymer templated in situ mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO₂) bubbles and showed excellent echo persistence. In vivo results demonstrated that the DOX-CaCO₃-MNPs generated CO₂ bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO₃-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO₂ bubbles necessary for US contrast. The DOX-CaCO₃-MNPs could also trigger the DOX release simultaneously with CO₂ bubble generation at the acidic tumoral environment. The DOX-CaCO₃-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers.