Ultrasound-Visualized Cuproptosis in Glioblastoma via Endogenous Copper Sequestration and Nitric Oxide-Gas Controlled Release Using a Programmable Nanoliposomal Platform

and ISDN-derived NO deplete GSH while suppressing ATP7B efflux pumps, amplifying copper overload to trigger lipoylated protein aggregation and Fe-S cluster degradation. Notably, NO-generated ultrasound contrast enables spatiotemporal mapping of copper transport dynamics. In vivo, DSF/S1P/ISDN-Lipos demonstrated favorable biosafety and significantly suppressed orthotopic glioblastoma growth. This work presents a theranostic approach for metal homeostasis regulation, where gas therapy synergizes with endogenous metallo-reprogramming to overcome adaptive resistance.