Nanomedicine strategies for disulfidptosis activation in SLC7A11-high tumors

Disulfidptosis is a recently identified form of regulated cell death (RCD) characterized by aberrant disulfide bond accumulation and cytoskeletal collapse under conditions of redox imbalance. SLC7A11-overexpressing tumors are uniquely susceptible to this pathway due to their elevated cystine uptake and dependence on glucose-driven NADPH production for redox maintenance. These metabolic liabilities create therapeutic opportunities to selectively trigger disulfidptosis via pharmacologic or material-based interventions. In this review, we provide a brief overview of the molecular basis and metabolic vulnerabilities underlying disulfidptosis and highlight emerging nanomedicine strategies designed to activate this mechanism. Nanoparticle-based systems have been developed to modulate SLC7A11 activity, inhibit glucose or NADPH supply, or amplify intracellular disulfide stress. We categorize these platforms into three mechanistic classes and discuss their design principles and functional outcomes. By integrating redox biology with smart delivery technologies, nanomedicine offers a promising route to exploit disulfidptosis for cancer therapy, particularly in tumors resistant to conventional treatments.