Antioxidant Mo₂C Nanosheets For Treatment Of Diabetic Wound Healing And Idiopathic Pulmonary Fibrosis

Reactive oxygen species（ROS）mainly include superoxide radicals(O2^·-),hydroxyl radicals（·OH）, singlet oxygen（¹O2）,H2O2 and other oxygen-containing reactive species,which play important physiological functions in living systems.Overexpression of ROS can lead to oxidative stress,cause local tissue damage,and result in the occurrence of various diseases.Although many antioxidant molecules and natural enzymes are able to reduce ROS levels,they often have inherent limitations such as low ROS scavenging capacity and insufficient stability in the physiological environment.In recent years,the emergence of enzyme-like catalytic or antioxidant nanomaterials with ROS modulation ability has provided a new way for alleviating oxidative stress damage.MXene,as a novel two-dimensional material with high specific surface area,abundant surface functional groups,mixed valence transition metals and highly active surface,exhibits potentially efficient enzyme-like catalytic activity and antioxidant capacity.Moreover,most MXene has high biosafety and easy degradability,which is expected to be a promising nano-biotherapeutic agent.This article aims to synthesize few-layer Mo₂C nanosheets（NSs）with high efficiency and broad-spectrum antioxidant activity,reveal the ROS scavenging activity and mechanism of action of Mo₂C nanosheets,explore the application of Mo₂C NSs in alleviating oxidative stress damage and promoting the treatment of diabetic trauma and pulmonary fibrosis,and provide new materials and new ideas for the treatment of ROS-related diseases.The specific research is as follows:1.Preparation,characterization,antioxidant activity and mechanism of Mo₂C nanosheets:Few-layer Mo₂C NSs were prepared from Mo₂Ga₂C precursor by high-temperature etching and intercalation exfoliation.AC-TEM,FTIR,XPS and EPR results showed that Mo₂C NSs have a large number of defective sites and abundant functional groups on the surface,and Mo exists in multiple valence states.Thanks to the unique structure of the material,Mo₂C can remove free radicals and ROS such as ABTS^+·,DPPH^·,H2O2,¹O2,O2^·-,·OH etc,and its ROS scavenging activity did not decrease significantly within 60 days.The clearance activity of Mo₂C for·OH is 150-6600 times higher than that of reference materials（Ti₃C₂,V₄C₃,TA,AA）,exhibiting broad-spectrum,efficient and long-lasting antioxidant capacity.The excellent antioxidant activity of Mo₂C can be attributed to multifaceted antioxidant mechanisms such as valence state engineering and surface engineering-driven electron transfer,hydrogen atom transfer,enzyme-like catalysis,etc.In addition,the reaction between Mo₂C and ROS resulted in structural fragmentation of Mo₂C,exhibiting high biocompatibility.2.Multifunctinal Mo₂C nanosheets with anti-inflammatory,anti-apoptotic and pro-angiogenesis effect for treatment of diabetic wounds:Excessive ROS,hypoxia,persistent inflammation,and impaired angiogenesis are important issues that impede diabetic wound healing,among which ROS clearance is the key to wound healing.Thanks to its unique structure,Mo₂C not only has efficient and broad-spectrum ROS scavenging capacity,but also promotes oxygen supply.Mo₂C-TA has been verified to be effective for treating diabetic wounds both in vitro and in vivo.Cellular experiments showed that Mo₂C-TA was non-significantly cytotoxic,the hemolysis ratio was less than 2%,it was non-sensitizing to the skin,and the in vitro ROS scavenging efficiency reached 89%,which was favorable to cell survival and proliferation.A streptozotocin（STZ）induced diabetic mouse model with full-layer wound injury was constructed in vivo.ELISA,Immunofluorescence,Western blot,and RT-q PCR revealed that Mo₂C-TA could reduce the expression of pro-inflammatory factors factor TNF-α,protein CD86（M1 macrophage marker）and i NOS（nitric oxide synthase gene:M1 signaling pathway key gene）,suppress the expression of intrinsic and extrinsic apoptotic pathways such as Cytc,caspase 9,caspase 3（cysteine aspartate proteinase）and increase the expression of CD31（platelet endothelial cell adhesion molecule）and VEGF（vascular endothelial growth factor）.These results reveal that Mo₂C-TA has multiple effects,which can promote macrophage polarization towards an M2（anti-inflammatory）phenotype,,suppressing cell apoptosis,promoting cell proliferation,migration,and angiogenesis,and promoting collagen deposition,thus achieving the effect of accelerating wound healing.This study provides a new idea for the development of multifunctional antioxidant nanomaterials to accelerate wound healing and treat ROS-related multi-factor diseases.3.Mo₂C reshapes redox homeostasis for the treatment of pulmonary fibrosis:Idiopathic pulmonary fibrosis is a chronic interstitial lung disease that is closely associated with oxidative stress.Antioxidant therapy is considered an effective strategy for preventing and treating pulmonary fibrosis.Mo₂C-TA has strong ROS scavenging ability,which can protect biomacromolecules such as liposomes from oxidative stress damage,reduceα-SMA expression,and inhibit fibroblast-to-myofibroblast transition.In a mouse model of pulmonary fibrosis induced by bleomycin,Mo₂C-TA reduced the expression of inflammatory factors TNF-αand TGF-β1,reshaped the SOD,CAT,and GSH activity in the organism,and reduced the expression ofα-SMA and Collagen I,achieving the effect of alleviating pulmonary fibrosis.Furthermore,Mo₂C-TA can transform from a a sheet-like structure into fragmented particles under physiological conditions,reaching the maximum amount excreted by the kidney within 12 h,showing low toxic effects on other organs at first.This work provides new materials and new ideas for oxidative stress-mediated fibrosis treatment.