Quercetin-loaded Ti3C2Tx MXene nanosheets enhance chemo-photothermal therapy in gastric cancer

Abstract

Gastric cancer is one of the most common malignancies of the digestive system. Although quercetin exhibits promising antitumor properties, its clinical application is limited by poor bioavailability, low water solubility, and chemical instability. Here, we employed mono- or few-layer Ti3C2Tx MXene nanosheets as carriers for the co-delivery of quercetin (as a chemotherapeutic agent) and MXene (as a photothermal therapy agent), aiming to achieve synergistic chemo–photothermal therapy against gastric cancer. Quercetin was successfully loaded onto Ti3C2Tx MXene nanosheets (MX-Que), as confirmed by various characterization techniques. The antitumor effects of MX-Que were evaluated using CCK-8 assays and reactive oxygen species (ROS) generation assays. Apoptosis was assessed via flow cytometry and further confirmed by analyzing apoptotic biomarkers. Ferroptosis was investigated by measuring intracellular iron levels and detecting ferroptosis-related biomarkers through Western blotting. MX-Que demonstrated high photothermal conversion efficiency under near-infrared (NIR) irradiation and enhanced quercetin release in response to NIR, leading to increased ROS production, apoptosis, and ferroptosis in gastric cancer cells. Furthermore, in a tumor-bearing mouse model, MX-Que administration followed by NIR irradiation significantly inhibited tumor growth and induced ferroptosis in vivo. These findings suggest that MX-Que holds great potential as a multifunctional nanoplatform for chemo–photothermal therapy of gastric cancer.

Keywords

• Gastric cancer
• Chemo-photothermal therapy
• Ti3C2Tx MXene
• Quercetin
• Ferroptosis