Inhibition of Post-Surgical Tumor Recurrence by 3-Bromopyruvate-Conjugated Gold Nanoclusters via MAPK and PI3K-Akt Pathways

The multitargeted strategy demonstrates significant potential in modern medical treatment, enhancing efficacy and reducing the risk of drug resistance. The rational combination design of nanomaterials and small molecules expands the new prospects of multitargeted therapies. Here, we have covalently linked ligands of atomic gold nanoclusters with 3-bromopyruvate and strategically designed a multitargeted approach to prevent postsurgical melanoma recurrence by activating the mitogen-activated protein kinase pathway and downregulating the phosphatidylinositol 3-kinase pathway. <i>In vitro</i> and <i>in vivo</i> validations confirm safety and outstanding efficacy, with recurrence rates reduced to 0% in completely resected mouse tumor models from 100%. The surface ligand modifiability of gold nanoclusters enables the precise engineering of nanodrugs with a molecule-like structure, providing a novel template that aligns with the clinical translation criteria set by the FDA. These findings identify an effective multitargeted strategy to develop structurally well-defined gold nanocluster-modified drug molecules in preventing postsurgical tumor recurrence.