Core-shell structured CeO₂@ZIF-8 nanohybrids regulating the Ce(III)/Ce(IV) valence conversion to enhance ROS-scavenging capacity for periodontitis treatment.

Abstract

Colonization of pathogenic microorganism is the initiating factor of periodontitis, inflammatory-induced imbalance of reductant-oxidant homeostasis is the leading cause of alveolar bone defects. Herein, core-shell structured nanohybrids with antibacterial, antioxidative and osteogenic properties were constructed by in situ growth of ZIF-8 nanocrystals onto cerium oxide nanoparticles (CeO₂@ZIF-8). The Ce³⁺/Ce⁴⁺ ratio can be manipulated via regulating the ZIF-8 shell thickness. The shell thickness increased with elevated concentration of Zn²⁺ that coordinated with organic linker in the synthesis process, leading to enhanced Ce³⁺/Ce⁴⁺ ratio in CeO₂@ZIF-8, which further promoted its antioxidative enzyme mimetic activities as well as osteogenic property. In vitro, CeO₂@ZIF-8 exhibited excellent antibacterial activities, provided cellular protective effect under oxidative stress state, and facilitated osteogenic differentiation. In vivo, CeO₂@ZIF-8 could alleviated bacterial infection induced inflammation response and promoted alveolar bone regeneration. The underlying mechanism was explored via bioinformatic analysis, which indicated that CeO₂@ZIF-8 promoted the expression of copper-zinc superoxide dismutase (SOD1) via upregulating oxidoreductase activity, so that to relive the oxidative stress and upregulate the expression of osteogenesis related genes and proteins. The above findings indicated that CeO₂@ZIF-8 could simultaneously achieve bacteriostasis, ROS scavenging and osteogenesis, so that to completely fulfill the therapeutic demand in the treatment of periodontitis.