Fig. 2

Gasdermin-E mediated pyroptotic cell death and immune cell activation using nanoparticle-based treatments. The association of therapies is essential for a successful anti-cancer treatment. Nanoparticles arise as a key to drug delivery and mitigation of chemotherapy-related collateral effects. The use of nanoparticles to promote chemotherapeutic agents’ delivery associated with the induction of pyroptosis has been explored as an important therapeutic strategy targeting cancer. GSDME is usually silenced in tumors and the encapsulation of some chemo drugs can result in the demethylation of GSDME encoding genes resulting in tumor cell pyroptosis. Another mechanism that has already been described for nanoparticle-based drug delivery is the induction of mitochondrial ROS leading to the liberation of Cytochrome c (Cyt c). These mitochondrial alterations result in the activation of caspase 3 that cleaves GSDME, also culminating in pore formation and pyroptosis. This lytic and inflammatory cell death suppresses tumor growth, decreases metastatic nodules, and enhances immune cells’ activation and anti-tumor immune response