Nonmetal Graphdiyne Nanozyme-Based Ferroptosis-Apoptosis Strategy for Colon Cancer Therapy

Ferroptosis-apoptosis, a new modality of induced cell death dependent on reactive oxygen species, has drawn tremendous attention in the field of nanomedicine. A metal-free ferroptosis-apoptosis inducer was reported based on boron and nitrogen codoped graphdiyne (BN-GDY) that possesses efficient glutathione (GSH) depletion capability and concurrently induces ferroptosis by deactivation of GSH-dependent peroxidases 4 (GPX4) and apoptosis by downregulation of Bcl2. The high catalytic activity of BN-GDY is explicated by both kinetic experiments and density functional theory (DFT) calculations of Gibbs free energy change during hydrogen peroxide (H₂O₂) decomposition. In addition, a unique sequence Bi-Bi mechanism is discovered, which is distinct from the commonly reported ping-pong Bi-Bi mechanism of most peroxidase mimics and natural enzymes. We anticipate that this nonmetal ferroptosis-apoptosis therapeutic concept by carbon-based nanomaterials would provide proof-of-concept evidence for nanocatalytic medicines in cancer therapy.