Synergistic Anticancer Therapy Via Injectable Nanoengineered Hydrogel-Mediated Disrupting of Redox Homeostasis and Induction of Ferroptosis/Apoptosis

In this study, we develop a hyaluronic-tannic acid (HA-TA) hydrogel loaded with Cu nanoparticles attach to MXene (MXene@Cu) to explore its potential as a targeted breast cancer treatment. The MXene@Cu nanosheets exhibit activity in depleting glutathione (GSH) and inducing reactive oxygen species (ROS) through the Fenton reaction. They can down-regulate the activity of glutathione peroxidase 4 (GPX4), leading to the accumulation of lipid peroxides (LPO) and inducing ferroptosis in tumor cells. GSH depletion enhances both ferroptosis and apoptosis efficacy. Additionally, under photothermal therapy (PTT), accelerated GSH consumption and the Fenton reaction further amplify ferroptosis and apoptosis. The nanoparticle-loaded hydrogel adheres to tumor tissue, enabling local treatment and precise PTT, thereby improving treatment efficiency. In summary, the MXene@Cu nanosheets synergistically enhance oxidative stress and consume GSH, triggering ferroptosis and amplifying photothermal-mediated apoptosis, leading to potent inhibition of breast cancer growth. This innovative therapeutic modality presents a promising approach for precise and effective local breast cancer treatment.