Single-atom Ca nanozyme induces glioma death through Ca2+-overload-enhanced catalytic tumor nanotherapy, ferroptosis and synergistic remodeling of the immune microenvironment.

In recent years, nanozyme-based catalytic therapy for tumors has garnered extensive attention. They combine the properties of nanomaterials and enzymes, precisely mimicking the structure of natural enzymes and exhibiting highly efficient catalytic ability. While nanozymes exert favorable catalytic therapeutic effects in the treatment of most tumors, their application in gliomas is limited by the unique physiological environment and the blood-brain barrier. In this study, a calcium atom nanozyme (CaCN) with peroxidase-like (POD-like) properties was developed. It can induce multiple cell death mechanisms in glioma cells, such as calcium overload and ferroptosis, and synergistically modulate the immune microenvironment. After being functionalized with transferrin (TF) targeting ligands and polyethylene glycol (PEG), it selectively crosses the blood-brain barrier, thereby inhibiting the malignant progression of glioma.