Spatial Au⁺ Mapping Reveals a Self-Amplifying Anti-Tumor Immunity Loop Driven by Au(I) Complexes

Although many metal complexes exhibit promising chemoimmunotherapeutic effects by inducing immunogenic cell death (ICD), the precise regulation of how these complexes interact with immune cells remains unclear. Herein, we introduced Au9 as the first representative gold complex to directly associate with immune cells in the tumor immune microenvironment (TIME). Our study delineated the mechanism underlying Au9-driven anti-tumor response and "hot" TIME remodeling, anchored in Au⁺ spatial mapping. Of note, macrophages, dendritic cells (DCs), and tumor cells ranked as the top three in Au⁺ enrichment. Further investigation showed that Au9 treatment stimulated the phagocytic activity of M1 macrophages, as confirmed by 3D scanning reconstructions. Importantly, Au9 treatment triggered a self-amplifying anti-tumor immunity loop. This study pioneered critical insights into the mechanisms of TIME-remodeling and laid the groundwork for the rational design of next-generation gold complexes with enhanced chemoimmunotherapeutic efficacy.