Near-infrared light-promoted multimodal synergistic targeted therapy for liver cancer based on copper-gold nanospheres-graphene nanocomposites.

Liver cancer is one of the most prevalent malignant tumors worldwide that poses significant challenges to conventional treatment due to issues such as poor biocompatibility, inadequate targeting, and the limited efficacy of single-agent therapies. These limitations can reduce treatment effectiveness and make accurate antitumor therapy more difficult. In recent years, the rapid development of multifunctional nanotechnology have substantially improved liver cancer treatment. This study designed folic acid (FA) and triformylcholic acid (TCA) targeted nanocomposites (GO-AuNSs-FA-TCA@BSA-Cu, GSFT@BCu) for liver cancer. This nanosystem integrates photothermal therapy (PTT), photodynamic therapy (PDT) and chemodynamic therapy (CDT) to construct a multimodal therapeutic platform, and introducing cuproptosis and apoptosis as a novel approach for precise modulation of tumor cell death. Transmission electron microscopy (TEM) and ultraviolet-visible (UV-Vis) spectroscopy were employed to characterize the morphological features and optical properties of the as-prepared nanocomposites. In vitro experiments confirmed that GSFT@BCu possessed a high photothermal conversion efficiency of 27.26% and can release copper ions in an NIR/GSH-responsive manner, further inducing oxidative stress and changes in mitochondrial membrane potential. In vivo liver cancer models showed that this combined multimodal therapy yielded a tumor inhibition rate of 82.47%. Additionally, the nanocomposite displayed outstanding blood compatibility and biosafety toward normal tissues. Overall, GSFT@BCu demonstrates excellent biocompatibility and prominent synergistic therapeutic effects against liver cancer, which providing a critical nanoplatform for multimodal synergistic therapy and precision medicine in oncology.