Cell Membrane-Camouflaged Gold Nanoclusters/Nanoflowers for Synergistic Ferroptosis-Like and Photothermal Therapy of Breast Cancer

Gold nanocluster (NC)-induced ferroptosis has emerged as a promising method for malignant tumors. However, the immune clearance and suboptimal reactive oxygen species (ROS) generation efficiency have limited its clinical application. Here, we engineered macrophage-membrane-coated gold nanocluster@nanoflower (CM-NC@NF) nanocomposites to address these challenges. In vitro studies demonstrated that the combination of NC and NF significantly enhanced ROS generation (∼9 times than NC), GSH depletion, and photothermal therapy (PTT) under laser irradiation, therefore promoting apoptosis in both 4T1 and MCF-7 cells. Furthermore, experimental evidence demonstrates that macrophage membrane encapsulation enables CM-NC@NF to evade clearance by immune cells. In the murine breast cancer model, CM-NC@NF exhibited significant tumor accumulation 4 h post-intravenous administration. Subsequent laser irradiation induced robust ROS generation and PTT within the tumor, leading to a tumor inhibition rate 5.7 times higher than that achieved with CM-NC alone. This therapeutic efficacy was further validated in an intra-tumoral injection experiment, showing a tumor inhibition rate 5.4 times higher than that of CM-NC alone. This multimodal strategy synergizes ferroptosis-like therapy with PTT, holding significant therapeutic promise for precision breast cancer treatment.