A Calcium Fluoride Nanozyme for Ultrasound‐Amplified and Ca²⁺‐Overload‐Enhanced Catalytic Tumor Nanotherapy

Abstract

The anticancer mechanism of nanozymes is dominantly associated with the capacity for generation of reactive oxygen species (ROS) caused by the valence change of metal elements. However, very little research is focused on and has achieved the exploration and development of enzyme‐mimicking activities of valence‐invariable metal compounds. Herein, a distinct valence‐invariable calcium fluoride (CaF2) nanozyme with ultrasound (US)‐enhanced peroxidase (POD)‐mimicking activity is rationally designed and engineered for efficient calcium (Ca2+)‐overload‐enhanced catalytic tumor nanotherapy, which is the first paradigm of Ca‐based nanozymes for catalytic cancer treatment. The release of exogenous Ca2+ ions from CaF2 nanocrystals and deleterious ROS generation derived from US‐amplified POD‐mimicking properties facilitate intracellular Ca2+ accumulation and achieve Ca2+‐overload‐induced mitochondrial dysfunction through introducing exogenous Ca2+ ions and regulating calcium‐pumping channels of neoplastic cells. Especially, US as an exogenous energy input is capable of substantially amplifying POD‐mimicking catalytic activities of CaF2 nanozyme, ultimately achieving efficient anti‐neoplastic outcome on both 4T1 breast tumor and H22 hepatic carcinoma animal models. Such a discovery of enzyme‐like activity of valence‐invariable metal compounds can broaden the cognition scope of nanozymes and effectively serves the field of catalytic and chemoreactive nanomedicine.

Hydrogen Sulfide Gas Amplified ROS Cascade: FeS@GOx Hybrid Nanozyme Designed for Boosting Tumor Chemodynamic Immunotherapy

“…The production of •OH was confirmed using electron paramagnetic resonance (Figure 2h). [26] This was also demonstrated by fluorescence spectroscopy using terephthalic acid as the detector (Figure S11, Supporting Information). Moreover, FeS@GOx showed significant and sustainable •OH production capacity when mixed with glucose, indicating its good cascade catalytic performance.…”

Biomineralized Polydopamine Nanoparticle-Based Sodium Alginate Hydrogels for Delivery of Anti-serine/Threonine Protein Kinase B-Rapidly Accelerated Fibrosarcoma siRNA for Metastatic Melanoma Therapy

“…B16F10 cells were used as the evaluation criteria, and a green fluorescence probe (Fluo-3 AM) was used to study the cellular calcium levels. It is acknowledged that an excessive amount of Ca 2+ may trigger Ca 2+ overload in cells to induce mitochondrial dysfunction (calcium ions interference therapy), which is recognized as a key factor in augmenting cell apoptosis. , Therefore, confocal laser scanning microscopy (CLSM) was first used to visualize B16F10 cells incubated with PBS (G1), PDA@CaP-SA (G2), PDA@siBRAF/CaP-SA (G3), and PDA@siBRAF/CaP-SA plus NIR (G4). As shown in Figure a, compared to the G1 group, the green Fluo-3 AM signals of Ca 2+ were increased in groups G2 and G3, confirming that Ca 2+ could release from the hydrogels following the degradation of CaP to affect cell function.…”

A Mitochondrial Perspective on Noncommunicable Diseases

“…Dong et al used harmless ultrasound as an external energy source to break through the tissue penetration depth and amplify the peroxidase-like catalytic activity of CaF2 to promote harmful ROS production and induce mitochondrial dysfunction induced by calcium overload in tumor cells and exerted significant antitumor effects in mammary tumors and hepatocellular carcinoma. The significant antitumor effects in animal models have broadened the ideas for nanoenzyme research [ 91 ].…”