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

Abstract

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.