Ultrasound-Augmented Mitochondrial Calcium Ion Overload by Calcium Nanomodulator to Induce Immunogenic Cell Death.

Immunogenic cell death (ICD), a manner of tumor cell death that can trigger antitumor immune responses, has received extensive attention as a potential synergistic modality for cancer immunotherapy. Although many calcium ion (Ca) nanomodulators have been developed for cancer therapy through mitochondrial Ca overload, their ICD-inducing properties have not been explored. Herein, an acid-sensitive PEG-decorated calcium carbonate (CaCO) nanoparticle incorporating curcumin (CUR; a Ca enhancer) (CaCUR) was prepared using a simple one-pot strategy. CaCUR served as not only a Ca nanomodulator inducing efficient mitochondrial Ca overload but also an ICD inducer during improved synergistic cancer therapy. Combination of CaCUR with ultrasound (US), CaCUR+US, led to an enhanced ICD effect attributable to the enhanced mitochondrial Ca overload, along with subsequent upregulation of reactive oxygen species levels. CaCUR also facilitates photoacoustic/fluorescence dual-mode imaging, as well as effectively suppressing tumor growth and metastasis, indicating promising theranostic properties.