Spray-Pyrolyzed Hollow and Yolk–Shell CeO ₂ Nanocarriers with Tunable Structure for Redox-Responsive Delivery and Gene Rescue Applications

High Resolution Image Download MS PowerPoint Slide Mesoporous CeO 2 nanoparticles (MCNs) are promising for biomedical applications because of their intrinsic redox activity and favorable biocompatibility. In particular, MCNs with hollow and yolk–shell nanostructures have attracted considerable interest as nanocarriers due to their large internal volume, tunable shell porosity, and ability to regulate mass transport. However, the synthesis of hollow and yolk–shell MCNs remains challenging using conventional solution-based methods. Here, we report a versatile gas-phase spray pyrolysis approach for the synthesis of MCNs with tunable structures via atomization of cerium nitrate solutions in the presence of polyvinylpyrrolidone (PVP) as a structure-directing agent. By systematically varying precursor composition, droplet size, and thermal processing conditions, the internal cavity formation, particle morphology, and mesoporous structure were precisely controlled. A custom-designed multizone furnace further enabled stepwise observation of particle formation, providing mechanistic insights into the morphological evolution during spray pyrolysis. Moreover, surface functionalization of MCNs with thiolated dextran introduced redox-responsive behavior through disulfide linkages that are cleavable under intracellular reductive conditions. Biological evaluation demonstrated excellent biocompatibility in HEK293 cells and revealed that the Rhodamine 6G loading efficiency strongly correlates with internal void volume and particle morphology. Furthermore, the functionalized MCNs significantly enhanced the efficacy of the aminoglycoside antibiotic G418, promoting translational readthrough in U2OS reporter cells and restoring CFTR-R553X activity in epithelial monolayers. These findings highlight spray-pyrolyzed mesoporous CeO 2 hollow and yolk–shell nanoparticles as promising redox-responsive nanocarriers for intracellular delivery and therapeutic modulation of genes affected by nonsense mutations.