2D Titanium-Based Nanozyme Induced a Ferroptosis-like Strategy for Triple-Negative Breast Cancer Therapeutics.

Abstract

Ferroptosis, a regulated cell death pathway driven by iron-dependent lipid peroxidation, has emerged as a promising strategy for cancer therapy. Nevertheless, the direct delivery of iron can lead to systemic toxicity. In this study, a nonferrous ferroptosis-like strategy employing 2D Ti₃C₂ MXene nanosheets was developed. The Ti₃C₂ nanozyme has been shown to possess peroxidase- and catalase-like activities, capable of decomposing H₂O₂ into cytotoxic·OH and O₂, respectively. When exposed to near-infrared II laser irradiation, Ti₃C₂ induced a localized increase in temperature and amplified reactive oxygen species production, resulting in a synergistic effect that led to mitochondrial damage and glutathione peroxidase 4 inactivation. In vivo studies demonstrated tumor suppression in triple-negative breast cancer (TNBC) models, accompanied by M1 macrophage polarization and CD8⁺ T cell activation. This work provides a novel paradigm for nanocatalytic ferroptosis therapy, combining enzymatic activity, photothermal effects, and immunomodulation to overcome TNBC resistance.