PLZ4@SeD

PLZ4@SeD is a targeted nanoparticle formulation designed for the treatment of bladder cancer. It consists of a nanoparticle shell functionalized with the PLZ4 ligand, which specifically targets bladder cancer cells, encapsulating the organoselenium derivative SeD-1b. The drug acts as a potent inducer of ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation. Mechanistically, PLZ4@SeD triggers robust production of reactive oxygen species (ROS) and iron mobilization by activating the oxidative phosphorylation (OXPHOS) regulatory axis. This leads to the depletion of glutathione (GSH) and the downregulation of glutathione peroxidase 4 (GPX4). Furthermore, PLZ4@SeD treatment suppresses PD-L1 expression and remodels the tumor microenvironment by increasing the infiltration of CD4+ and CD8+ T cells while reducing immunosuppressive macrophages. This dual-action approach sensitizes bladder cancer to chemotherapy (such as doxorubicin) and immunotherapy (such as anti-PD-1 therapy).