Multi-Organelle Stress-Induced Paraptosis by a ROS-Amplifying Nanocatalyst for Enhanced Cancer Immunotherapy - PubMed
3 days ago
- #immunotherapy
- #paraptosis
- #chemodynamic therapy
- Engineered porous Fe3O4 nanoplatform coated with Fe3+-tannic acid complex and loaded with CCCP and LOD to enhance CDT efficacy.
- Nanoplatform self-supplies H2O2 and blocks autophagic flux, triggering paraptosis, an unconventional cell death pathway.
- Acid-triggered dissociation releases Fe2+/Fe3+ for Fenton reactions, while LOD converts lactate to H2O2, overcoming H2O2 limitation.
- CCCP collapses mitochondrial membrane potential, amplifying ROS leakage and inducing oxidative storm.
- ROS surge causes mitochondrial dysfunction, ER stress, and suppressed autophagy, leading to paraptotic cell death with cytoplasmic vacuolization.
- Combined with αPD-L1, the nanoplatform activates antitumor immunity, suppressing primary and distant tumors.
- Pioneers paraptosis activation via iron-based nanodrug, redefining CDT through multi-organelle stress synergy for enhanced immunotherapy.