Morphology-controlled therapeutic activity of cerium oxide nanoparticles for mild traumatic brain injury

The design and optimization of nanostructures with unique morphologies and properties are at the forefront of biomedical nanotechnology. Cerium oxides are widely used to investigate the effect of morphology on performance. However, elucidating the morphology-activity relationship of cerium oxide nanocrystals in biomedical applications remains challenging. Herein, the therapeutic effects of cerium oxide nanoparticles with different morphologies: cerium oxide nanorods with two different aspect ratios (CeOx NRs_A and CeOx NRs_B), cerium oxide nanopolyhedra (CeOx NPs), and cerium oxide nanocubes (CeOx NCs) are investigated in in vivo and in vitro mild traumatic brain injury (TBI) models. Cerium oxide nanoparticles inhibit oxidative stress and inflammation after mild TBI, alleviating cognitive impairment; furthermore, the therapeutic effect is significantly affected by their morphology. Owing to the higher Ce3+/Ce4+ ratio, exposure of more active crystal surfaces, and greater number of exposed oxygen vacancies, CeOx NRs show better activity than CeOx NPs and CeOx NCs for mild TBI. Among the two investigated types of cerium oxide nanorods, CeOx NRs_A, with a higher Ce3+/Ce4+ ratio on the surface, appear to spread better than CeOx NRs_B in the injured lesions. The factors causing morphology-controlled biomedical performance, such as Ce3+/Ce4+ molar ratio, surface area, and aspect ratio, are discussed.