Structural,Enzyme-like Properties Of Atomic-Precision Clusters And Applications In Biomedicine

Nanozymes is a kind of nanomaterial who possesses natural-enzyme-like activity.Nanozyme is considered as most valuable extended application of nanomaterials.And nanozymes have attracted significant attention owning to their unique high,multiple activities and low cost.However,most of the reported nanozymes are nanoparticles(larger than 10 nm).Their unclear crystal structure induced ambiguous catalytic active sites and electronic transfer mechanism.Thus,the ultrasmall clusters with atomic precision have definite structure,which can obtain unique physical and chemical properties through modification and morphology control,and could overcome the shortcomings of large-scale nanoparticles.To date,few reports focus on reversible nanozymes.Herein,we report an atomic precision Mn₁₂ clusters show reversible enzyme-like activities and their catalytic activity has been further enhanced by Ni single atom doping.The dual effects of radiosensitization and radiation protection are demonstrated.The major achievements are as follows:(1)The Ni²⁺were introduced by a two-step synthesis reaction.The results of mass spectrometry exhibit the single-atom doping occurs with shifts in XRD patterns,obviously.XPS analysis showed that the average valence state of Mn increased after doping.XANES and EXAFS further confirmed the XPS results and showed that the doping occurs in the core.The single-atom Ni doped Mn₁₂ clusters show an enhanced oxygen evolution property with an improved overpotential of 275 m V.The OER activities in weak acid is 3.5 times higher than that in neutral environment,indicating the soluble Mn₁₂ clusters has strong oxidation ability in acid environment and can produce a lot of free radicals.(2)Importantly,the Mn₁₂ clusters can produce or clear hydroxyl radicals smartly under different p H.The ability of catalase like enzyme is also regulated by p H value,and the catalytic activity is about 6.2 times of that of weak acid.As such,Ni-doped Mn₁₂ clusters possess a unique p H-switchable feature where·OH are generated via AOPs at acidic and in turn scavenged at neutral,which showing reversible enzyme-like activities.The catalytic performance of Ni doped catalyst was improved by about 20%Density functional theory calculation shows Mn₁₂ clusters with the central replacement can form a stable structure and prefer to react with an oxygen atom with very low binding energy.(3)4T1 and CHO cells were employed to study radiation protection and radiosensitization effect in vitro.The results showed that Ni doped Mn₁₂ clusters could induce more apoptosis of cancer cells in the process of radiation while protective effect on normal cells.They also had ignorable biological toxicity.In vivo experiments further confirmed that the clusters have the dual effects of radiosensitization and radiation protection.Compared with the irradiation-only group,the tumor volume can be reduced by 45.3%under the radiation dose of 6.5 Gy,and the survival rate of the irradiated mice can reach 100%.