Glutathione S transferase assembled gold silver nanoclusters activate cGAS STING immunity in breast cancer

Breast cancer often returns or spreads after treatment, and therapies that can destroy tumors while also engaging the immune system are urgently needed. However, it remains difficult to design safe nanomaterials that both heat tumors under light and turn dying cancer cells into signals that support long-lasting antitumor immunity. Here we show that glutathione S-transferase guided self-assembly produces ultrasmall glutathione-stabilized gold-silver nanoclusters for laser-assisted breast cancer treatment. Under near-infrared light, these nanoclusters efficiently generate heat and oxidative stress, killing breast cancer cells and releasing immune-stimulating signals. The treatment activates the cGAS-STING immune signaling pathway, promotes dendritic cell maturation, increases tumor-killing T cell infiltration, and strengthens memory T cell responses. In mouse models of primary and metastatic breast cancer, the nanoclusters preferentially accumulate in tumors and suppress tumor growth, metastasis, and relapse with limited signs of toxicity. This protein-guided nanocluster strategy provides a potential route for combining localized light-based treatment with systemic antitumor immunity and may support the future development of safer and more durable cancer nanomedicines. GST-mediated self-assembly of gold-silver nanoclusters activates cGAS-STING signaling and remodels antitumor immunity, enabling photothermal-immunotherapy to inhibit breast cancer growth, metastasis and recurrence.