Calcium-Based Nanomedicine for Cancer Therapy

Calcium-based nanomedicine exploits the unique biological roles of Ca2+ ions and their capacity to modulate tumour cell biology when delivered in nanoscale vehicles. Such approaches typically employ calcium-containing materials—calcium carbonate, calcium peroxide, calcium phosphate or metal–organic frameworks—as pH-responsive or enzymatically responsive carriers. Upon accumulation in the acidic tumour microenvironment, these carriers release Ca2+ to induce mitochondrial dysfunction, trigger apoptosis or ferroptosis, and amplify oxidative stress through reactive oxygen species. Concomitantly, modulation of Ca2+ signalling can reprogramme the immune microenvironment by promoting dendritic cell maturation, macrophage polarisation and cytotoxic T-cell activity. Integration with external triggers such as near-infrared light or radiofrequency ablation further refines spatial control, enabling dual modalities of oxidative and ionic damage. Together, these strategies address drug resistance, minimise off-target toxicity and synergise with immunotherapies and checkpoint blockade, underscoring the global significance of calcium-based nanomedicine as a versatile, scalable platform for translational oncology.

Research from Nature Portfolio

One core-shell nanoagent integrates an iron(III) carboxylate metal–organic framework shell around an upconversion nanoparticle core to achieve near-infrared-triggered calcium influx and Fenton-type oxidative stress within mitochondria. Folate decoration on the framework enables selective uptake by tumour cells, where light-activated acidification and Fe3+ reduction provoke mitochondrial Ca2+ overload and lethal hydroxyl radical generation. This dual-damage system demonstrates potent antitumour effects in both cell models and patient-derived xenografts.

Another innovation harnesses calcium carbonate–assisted encapsulation of lipoxidase and hemin within a biodegradable polymeric nanoreactor to complement radiofrequency ablation. Upon tumour ablation, these nanoreactors utilise residual cellular debris to fuel lipid peroxidation, triggering ferroptosis in residual cancer cells and priming systemic antitumour immunity. In preclinical models, this approach suppresses recurrence and metastasis, and further potentiates immune checkpoint blockade.

Calcium-Based Nanomedicine for Cancer Therapy publication trend

The graph below shows the total number of articles in calcium-based nanomedicine for cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Calcium overload: Excessive intracellular Ca2+ concentration that disrupts mitochondrial function and triggers programmed cell death.

Tumour microenvironment (TME): The complex network of cancer cells, immune cells, extracellular matrix and biochemical factors surrounding a tumour.

Metal–organic framework (MOF): A porous coordination polymer composed of metal nodes and organic linkers, used as a nanocarrier for controlled release.

Ferroptosis: A form of regulated cell death driven by iron-dependent lipid peroxidation and oxidative damage.

Upconversion nanoparticles (UCNPs): Nanomaterials that absorb near-infrared light and emit higher-energy photons, enabling deep-tissue photoactivation.

References

1. MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload. Nature Communications (2021).
2. Tumor-killing nanoreactors fueled by tumor debris can enhance radiofrequency ablation therapy and boost antitumor immune responses. Nature Communications (2021).
3. Manipulating calcium homeostasis with nanoplatforms for enhanced cancer therapy. Exploration (2023).
4. Multifunctional Calcium–Manganese Nanomodulator Provides Antitumor Treatment and Improved Immunotherapy via Reprogramming of the Tumor Microenvironment. ACS Nano (2023).
5. Supramolecularly engineered bacteria mediated calcium overload and immunotherapy of tumors. Theranostics (2024).