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

• Published in: Nano letters Vol. 21; no. 5; pp. 2088 - 2093
• Main Authors: Zheng, Pan, Ding, Binbin, Jiang, Zhongyu, Xu, Weiguo, Li, Gao, Ding, Jianxun, Chen, Xuesi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.03.2021
• Subjects: Calcium nanomodulator; mitochondrial calcium ion overload; ultrasound; immunogenic cell death; immunotherapy
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/acs.nanolett.0c04778

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 (Ca2+) nanomodulators have been developed for cancer therapy through mitochondrial Ca2+ overload, their ICD-inducing properties have not been explored. Herein, an acid-sensitive PEG-decorated calcium carbonate (CaCO3) nanoparticle incorporating curcumin (CUR; a Ca2+ enhancer) (PEGCaCUR) was prepared using a simple one-pot strategy. PEGCaCUR served as not only a Ca2+ nanomodulator inducing efficient mitochondrial Ca2+ overload but also an ICD inducer during improved synergistic cancer therapy. Combination of PEGCaCUR with ultrasound (US), PEGCaCUR+US, led to an enhanced ICD effect attributable to the enhanced mitochondrial Ca2+ overload, along with subsequent upregulation of reactive oxygen species levels. PEGCaCUR also facilitates photoacoustic/fluorescence dual-mode imaging, as well as effectively suppressing tumor growth and metastasis, indicating promising theranostic properties.