IntroductionThe combination of photothermal therapy and chemotherapy has emerged as a promising strategy for cancer treatment. The green synthesis of gold nanoparticles (Au NPs) using extracts from traditional Chinese medicine Scutellaria barbata D. Don (Scu) has revealed an economical, sustainable, and eco-friendly approach for the outstanding anticancer activities. MethodsScu extract was mixed with HAuCl4 solution to fabricate Scu-Au NPs. The synthesis process was optimized by varying the reaction temperature, reaction time, and HAuCl4 concentration. The changes in the components of Scu before and after synthesis were analyzed using the 3,5-dinitrosalicylic acid (DNS) reduction test, the rutin colorimetric method, and the Folin–Ciocalteu method. The morphology, size, and structure of Scu-Au NPs were characterized by TEM, DLS, XRD, and XPS. The photothermal characteristics induced by near-infrared (NIR) irradiation were assessed by continuously monitoring the temperature elevation. The anticancer activity and mechanisms of Scu-Au NPs were investigated using MTT assay, cell uptake studies, ROS level detection, cell apoptosis and necrosis assays, flow cytometry analysis, intracellular Caspase-3 protein activity fluorescence detection, and Western blot analysis on A549, 4T1, and RAW264.7 cells. ResultsScu-Au NPs were successfully fabricated using Scu extract as a reducing agent. The Scu-Au NPs were spherical with a size of 50 nm. During the synthesis process, the levels of reducing sugars, flavonoids, and polyphenols in the Scu extract decreased by 80.8%, 54.3%, and 70.1%, respectively. Scu-Au NPs demonstrated excellent photothermal responsiveness, thermostability, and biocompatibility. For chemo-photothermal anticancer therapy, the cytotoxicity of Scu-Au NPs on 4T1 cells reached approximately 85% upon exposure to 808 nm NIR irradiation. The anticancer activity was attributed to the induction of apoptosis and necrosis, achieved by increasing intracellular ROS levels, causing cell cycle arrest at the S phase, and modulating the expression of apoptosis-related proteins. DiscussionOur synthesized Scu-Au NPs exhibit favorable photothermal conversion characteristics, demonstrating excellent therapeutic efficacy and safety for cancer treatment.