What question did this study set out to answer?

To develop an ultrasound-responsive nanomaterial for targeted tumor therapy and evaluate its effects on breast cancer cell death.

February 22, 2026Open Access

Ultrasound-Responsive Calcium Copper Phosphate Nanomaterials Induce Tumor Cell Death via the Synergistic Release of Copper and Calcium

Key Points

To develop an ultrasound-responsive nanomaterial for targeted tumor therapy and evaluate its effects on breast cancer cell death.
Developed Ca19Cu2(PO4)14 nanomaterials with a uniform morphology and crystalline structure.
Conducted in vitro studies using 4T1 metastatic breast cancer cells with and without ultrasound exposure.
Measured apoptosis rates and cell viability at various concentrations of Ca19Cu2(PO4)14.
Analyzed cellular mechanisms of action by evaluating mitochondrial stress and metabolic homeostasis.
Ca19Cu2(PO4)14 combined with ultrasound led to 37.56% apoptosis in 4T1 cells at 20 μg/mL.
Cell viability was reduced to 41.37% in treated cells, while nanomaterials alone showed negligible cytotoxicity.
Mitochondrial stress was linked to the suppression of a copper/redox regulator and the PDH complex.

Abstract

Metastatic breast cancer remains a significant therapeutic challenge due to its high invasiveness and resistance to conventional treatments. In this study, an ultrasound-responsive copper-calcium phosphate (Ca19Cu2(PO4)14) nanomaterial is developed for synergistic ion-mediated tumor therapy. The Ca19Cu2(PO4)14 nanomaterials exhibit a uniform morphology and crystalline structure, as well as good colloidal stability. Upon ultrasound irradiation, the release of Cu2+ and Ca2+ is spatiotemporally controlled via mechanical and cavitation effects. In vitro studies using highly metastatic 4T1 cells demonstrate that a combination of Ca19Cu2(PO4)14 and ultrasound significantly enhances apoptosis to 37.56%, while inducing 41.37% cell viability at 20 μg/mL of Ca19Cu2(PO4)14+ US. In contrast, Ca19Cu2(PO4)14 alone exhibits negligible cytotoxicity. Mechanistic investigations reveal that the combined release of Cu2+ and Ca2+ induces pronounced mitochondrial stress by suppressing the mitochondrial copper/redox regulator FDX1 and the PDH complex E2 subunit DLAT, thereby impairing mitochondrial metabolic homeostasis and promoting mitochondrial dysfunction. Overall, this study presents an ultrasound-triggered Ca19Cu2(PO4)14 nanoplatform for the effective ablation of tumor cells.

Ultrasound-Responsive Calcium Copper Phosphate Nanomaterials Induce Tumor Cell Death via the Synergistic Release of Copper and Calcium

Key Points

Abstract

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