Unlocking the Potential of Disulfidptosis: Nanotechnology-Driven Strategies for Advanced Cancer Therapy

Abstract

Tumor tissues exhibit elevated oxidative stress, with the cystine-glutamate transporter xCT solute carrier family 7 member 11 (xCT/SLC7A11) protecting cancer cells from oxidative damage by facilitating cystine uptake for glutathione synthesis. Disulfidptosis, a newly identified form of programmed cell death (PCD), occurs in cells with high xCT/SLC7A11 expression under glucose-deprived conditions. Distinct from other PCD pathways, disulfidptosis is characterized by aberrant disulfide bond formation and cellular dysfunction, ultimately resulting in cancer cell death. This novel mechanism offers remarkable therapeutic potential by targeting the inherent oxidative stress vulnerabilities of rapidly growing cancer cells. Advances in nanotechnology enable the development of nanomaterials capable of inducing reactive oxygen species (ROS) generation, disrupting disulfide bonds. In addition, they are capable to deliver therapeutic agents directly to tumors, thereby improving therapeutic precision and minimizing off-target effects. Moreover, combining disulfidptosis with ROS-induced immunogenic cell death can remodel the tumor microenvironment and enhance anti-tumor immunity. This review explores the mechanisms underlying disulfidptosis, its therapeutic potential in cancer treatment, and the synergistic role of nanotechnology in amplifying its effects. Selective induction of disulfidptosis using nanomaterials represents a promising strategy for achieving more effective, selective, and less toxic cancer therapies.