Photosensitizer-loaded bubble-generating mineralized nanoparticles for ultrasound imaging and photodynamic therapy

In this work, we have developed photosensitizer-loaded bubble-generating calcium carbonate (CaCO₃)-mineralized nanoparticles that have potential for ultrasound imaging (US)-guided photodynamic therapy (PDT) of tumors. A photosensitizer, chlorin e6 (Ce6)-loaded CaCO₃-mineralized nanoparticles (Ce6-BMNs), was prepared using an anionic block copolymer-templated in situ mineralization method. Ce6-BMNs were composed of the Ce6-loaded CaCO₃ core and the hydrated poly(ethylene glycol) (PEG) shell. Ce6-BMNs exhibited excellent stability under serum conditions. Ce6-BMNs showed enhanced echogenic US signals at tumoral acid pH by generating carbon dioxide (CO₂) bubbles. Ce6-BMNs effectively inhibited Ce6 release at physiological pH (7.4). At a tumoral acidic pH (6.4), Ce6 release was accelerated with CO₂ bubble generation due to the dissolution of the CaCO₃ mineral core. Upon irradiation of Ce6-BMN-treated MCF-7 breast cancer cells, the cell viability dramatically decreased with increasing Ce6 concentration. The phototoxicity of the Ce6-BMNs was much higher than that of free Ce6. On the basis of tumoral pH-responsive CO₂ bubble-generation and simultaneous Ce6 release at the target tumor site, these CaCO₃ mineralized nanoparticles can be considered as promising theranostic nanoparticles for US imaging-guided PDT in the field of tumor therapy.