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

Abstract

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 2+ ) nanomodulators have been developed for cancer therapy through mitochondrial Ca 2+ overload, their ICD-inducing properties have not been explored. Herein, an acid-sensitive PEG-decorated calcium carbonate (CaCO 3 ) nanoparticle incorporating curcumin (CUR; a Ca 2+ enhancer) ( PEG CaCUR) was prepared using a simple one-pot strategy. PEG CaCUR served as not only a Ca 2+ nanomodulator inducing efficient mitochondrial Ca 2+ overload but also an ICD inducer during improved synergistic cancer therapy. Combination of PEG CaCUR with ultrasound (US), PEG CaCUR+US, led to an enhanced ICD effect attributable to the enhanced mitochondrial Ca 2+ overload, along with subsequent upregulation of reactive oxygen species levels. PEG CaCUR also facilitates photoacoustic/fluorescence dual-mode imaging, as well as effectively suppressing tumor growth and metastasis, indicating promising theranostic properties.

The Role of Tumor Inflammatory Microenvironment in Lung Cancer

“…It mainly includes tumor cells, tumor-associated fibroblasts, immune cells, vascular endothelial cells, extracellular matrix (ECM) and its degrading enzymes, various growth factors, and inflammatory factors. Moreover, it has special physical and chemical characteristics (e.g., hypoxia, low pH) (Wang et al, 2016;Wang et al, 2019;Jiang et al, 2020;Zheng et al, 2020;Liu et al, 2021;Song et al, 2021;Zheng et al, 2021). The TME has multiple effects on tumor initiation, development, and progression, and the mechanism is complex.…”

Transformable Nanosensitizer with Tumor Microenvironment‐Activated Sonodynamic Process and Calcium Release for Enhanced Cancer Immunotherapy

“…[19] Imbalance of intracellular Ca 2+ disturbs oxidative phosphorylation and elevates ROSg eneration to generate cellular damage. [20] Therefore,…”

Polymeric Nanosystems for Immunogenic Cell Death‐Based Cancer Immunotherapy

“…Our group has Reproduced with permission. [113] Copyright 2021, American Chemical Society. constructed various therapeutic materials for bone repair [114] or cancer therapy [115] by the utilization of nanocomplex or scaffolds.…”

“…Zheng and co‐workers constructed a curcumin (CUR)‐loaded calcium carbonate (CaCO 3 ) nanosystem ( PEG CaCUR) via a facile one‐pot method. [ 113 ] The CUR could upregulate the amount of Ca 2+ in the mitochondria through inducing the arrival of Ca 2+ at cytoplasm from endoplasmic reticulum. The use of ultrasound (US) was not only beneficial for cell uptake but also increase Ca 2+ concentration, which accompanies with generation of ROS.…”

“…d) Treatment scheme using animal model. e) Populations of immune cells in draining lymph nodes after different treatments.Reproduced with permission [113]. Copyright 2021, American Chemical Society.…”