Hollow, Rough, and Nitric Oxide-Releasing Cerium Oxide Nanoparticles for Promoting Multiple Stages of Wound Healing

Abstract

Wound healing is a complex and sequential biological process that involves multiple stages. Although various nanomaterials are applied to accelerate the wound healing process, only a single stage is promoted during the process, lacking hierarchical stimulation. Herein, hollow CeO₂ nanoparticles (NPs) with rough surface and l-arginine inside (_AhCeO₂ NPs) are developed as a compact and programmable nanosystem for sequentially promoting the hemostasis, inflammation, and proliferation stages. The rough surface of _AhCeO₂ NPs works as a nanobridge to rapidly closure the wounds, promoting the hemostasis stage. The hollow structure of _AhCeO₂ NPs enables the multireflection of light inside particles, significantly enhancing the light harvest efficiency and electron–hole pair abundance. Simultaneously, the porous shell of _AhCeO₂ NPs facilitates the electron–hole separation and reactive oxygen species production, preventing wound infection and promotion wound healing during the inflammation stage. The enzyme mimicking property of _AhCeO₂ NPs can alleviate the oxidative injury in the wound, and the released l-arginine can be converted into nitric oxide (NO) under the catalysis of inducible NO synthase, both of which promote the proliferation stage. A series of in vitro and in vitro biological assessments corroborate the effectiveness of _AhCeO₂ NPs in the wound healing process.