Preparation Of Multifunctional Nanomaterials Based On CeO₂ And Application In Treatment For Nasal Polyps

Excessreactive oxygen species?ROS?-triggered oxidative stress is associated with numerous diseases,covering inflammation and cancer,etc.Inflammation is a biological defense response of the living body to external stimuli.Nasal polyps is a chronic inflammation that still has a tendency to recur after medical and surgical treatment,which greatly decreases the quality of life.Since the efficacy of current therapeutic methods is limited,it is urgent to develop a novel strategy to realize the multi-modality anti-inflammatory treatment.Recently,nanozymes have received great attention due to the excellent physicochemical properties and large specific surface area.In this study,we have developed a simple and repeatable method to make multi-functional Au-CeO₂ JNPs,which can eliminate multiple ROS in vitro and in cells,load and continuously release anti-inflammatory drug?Danshensu sodium salt?,and can be applied to X-ray computed tomography?CT?imaging guided "nanozymes-drug" synergistic anti-inflammatory treatment of nasal polyps.In addition,because of two synergistic effects: the synergistic ROS scavenging properties between the Au and CeO₂ domains as well as the synergistic antioxidant effect between anti-inflammatory drug and the entire nanozymes?Au-CeO₂ JNPs?,compared with individual CeO₂ NPs and Au-CeO₂ JNPs,the same concentration of Danshensu sodium salt?DSS?loaded Au-CeO₂ JNPs showed stronger anti-inflammatory performance.Importantly,the levels of ROS and pro-inflammatory cytokines mRNAs?IL-1? and IL-6?decreased after the primary human nasal polyps epithelial cells?HNECs?treated with Au-CeO₂ JNPs,indicating the potential therapeutic effect of nasal polyps.Therefore,this novel nanozymes-drug synergistic nanosystem provided a new concept and approach in the progress of anti-inflammation.In the following work,hollow CeO₂ NPs were synthesized using SiO₂ NPs as a template.Next,the CeO₂@PAA NPs were prepared.Then,Mn²⁺was hydrolyzed on PAA to obtain CeO₂@PAA-Mn NPs.Finally,PDA NPs were formed on the PAA-Mn NPs through the self-polymerization of DA to obtain the CeO₂@PAA-Mn@PDA NPs.After washing,the CeO₂@PDA yolk-shell nanobowls were obtained.The PDA NPs and Mn elements can be used for PA and MR imaging,respectively.The bowl-shaped structure of PDA and the hollow structure of CeO₂ can be used for DSS loading.The CeO₂@PDA yolk-shell nanobowls can be used for eliminating multiple ROS in vitro,PA and MR dual-mode imaging guided the removal of ROS in HNECs and down-regulating the expression of pro-inflammatory cytokines mRNAs?IL-1? and IL-6?.Additionally,this "yolk-shell" structured composite nanomaterials combine antioxidant CeO₂ nanozymes with non-enzymatic antioxidant biomolecules PDA,which have synergistic treatment effects for nasal polyps and enhanced antioxidant properties than a single nanomaterial.