Cell death fate switching through organelle-precision thermal control over mitochondrial dynamics

Organelle-precision photothermal therapy (OPTT) is widely used for disease treatment with fewer side effects, but its potential to manipulate organelle dynamics is not fully understood. This study investigates how OPTT-induced PANoptotic cell death regulates inter-mitochondrial behaviors using gold nanorods. We show that localized heat stress prompts initial mitochondrial network fusion followed by hyper-fission, disrupting homeostasis and increasing sensitivity to chemotherapeutics. Both non-specific and mitochondria-targeted OPTT were analyzed, revealing the importance of mitochondrial dynamics in determining cell fate. Our results indicate that modulating these dynamics can control cell death and immune responses, highlighting the promise of nanotherapeutic approaches for enhancing cancer therapies.