A Hybrid Alloying Nanozyme-Glutathione Inhibitor Co-Delivery System Initiates a Dual-Disruption on Cancer Redox Homeostasis

Altered redox homeostasis has long been observed in cancer cells, which can be exploited for therapeutic benefits. However, reactive oxygen species (ROS) pleiotropy coupling with reductive adaptation in cancer cells poses a formidable challenge for redox dyshomeostasis-based cancer therapy. Herein, a AuPd alloying nanozyme-glutathione (GSH) biosynthesis inhibitor co-delivery system (B-BMES) is developed using dendritic SiO 2 as a matrix to target cancer redox homeostasis. By optimizing element composition, the alloying nanozyme in B-BMES exhibits a potent peroxidase (POD)-like activity to trigger ROS insults-mediated redox dyshomeostasis. Such a POD functionality is attributed to the optimized electronic structure and catalytic activity. Simultaneously, the B-BMES abrogates the reductive adaptation by exerting its molecule-targeted GSH suppression, thereby achieving a dual-disruption on cancer redox homeostasis. Camouflaging B-BMES with tumor-homologous cytomembrane, a hybrid nanosystem with biological stability and tumor-targeting ability is further fabricated, which initiates a safe, precise redox disruption-based cancer therapy and sensibilizes standard chemotherapy.