Large-sized and highly crystalline ceria nanorods with abundant Ce3+ species achieve efficient intracellular ROS scavenging.

Abstract

Intracellular reactive oxygen species (ROS) are associated with various inflammatory physiological processes and diseases, highlighting the need for their regulation to mitigate the detrimental effects of oxidative stress and to reduce cellular damage and disease progression. Here, we demonstrate cerium oxide (ceria) nanorods synthesized using a sol-gel method followed by heat treatment, called "AHT-CeNRs", as an efficient intracellular ROS scavenger. The synthesized AHT-CeNRs exhibited exceptional superoxide dismutase (SOD) and catalase (CAT)-like activities, both of which are crucial for converting ROS into harmless products. This was attributed to their high crystallinity, large surface area, numerous defects including oxygen vacancies, and abundant Ce³⁺ species. AHT-CeNRs exhibited higher CAT-like activities than natural CAT and conventional nanozymes, with a more than five-fold lower K_m. When tested on HaCaT human keratinocyte cells, AHT-CeNRs primarily localized to the membrane but effectively scavenged intracellular ROS, potentially through their transmembrane catalytic action without disrupting the membrane. This contrasts with conventional antioxidant nanoparticles that act within the cytosol after penetrating the plasma membrane. AHT-CeNRs maintained cell viability by efficiently scavenging ROS, resulting in approximately 4-fold and 2-fold lower levels of inducible nitric oxide synthase (iNOS) and lactate dehydrogenase (LDH) compared to those in ROS-induced inflammation-stimulator lipopolysaccharide (LPS)-treated control groups, respectively. This simple yet effective method for intracellular ROS scavenging using AHT-CeNRs holds great potential for applications in cell and in vivo therapeutics to regulate intracellular ROS levels.