Controllable Preparation Of Single-atom Catalysts For Tumor Catalytic Therapy

Nano-catalysts plays a key role in the development of chemical manufacturing,energy conversion,storage,biomedicine,and many other fields.Nanoparticle catalysts(nanozymes)can kill tumors by activating small molecules such as O2,H2O,and H2O2 to generate toxic free radicals,achieving good therapeutic effects in the field of tumor treatment.However,they have disadvantages of poor selectivity,unclear reaction mechanism,and difficulty in activity regulation due to the complex structure and composition of nanozymes,which restrict their development in the field of catalytic therapy.Therefore,the construction of catalysts with high activity,high selectivity,clear active sites and low price plays a key role in the activation of small molecules.Recently,the development of single-atom catalysts(SACs)provides a great platform for the overcome of these limitations.SACs have the characteristics of atomic dispersion and simple coordination,which enable the high atomic utilization and catalytic selectivity,clear catalytic sites of the SACs,thus providing a way to study the catalytic mechanism.SACs have the advantages of both nanozymes and natural enzymes,such as outstanding activity,great stability,and high recovery rate.Therefore,we can rationally design SACs to obtain excellent enzyme-like activity to achieve better catalytic therapy effects.The catalytic performance of SACs is closely related to the utilization of surface metal atoms,the number of active sites,the stability and coordination structure of single-atom sites.Recent studies have shown that the increase of the specific surface area and the surface defect are effective ways to improve the atomic utilization and the density of active sites.When the single atom loading was increased,it is particularly important to effectively prevent the aggregation of single metal atoms to achieve highest atom utilization efficiency.In addition,through strong support-metal interactions(SMSI),the support of SACs can effectively alter the electronic properties of the active sites,which could facilitate electron transfer during chemical reactions.Then optimized adsorption/desorption energies of intermediate species were endowed,and thus significantly enhancing the catalytic performance.Therefore,selecting suitable supports and using effective methods to anchor single-atom catalysts with improved catalytic performance is the key point for the synthesis and application of singleatom catalysts.In this paper,SiO2 nanomeshes(NMs)with ultrashort ordered channels to anchor cobalt single atoms were designed,and obtained highly stable and active SACs.Therefore,it is an effective way to improve the stability and catalytic activity of SACs by adjusting the defect concentration and specific surface area of the carrier.On this basis,Ru SACs supported by defect-rich carbon dots and Ni SACs supported by sulfur-modified defect-rich carbon frameworks were obtained by rationally designing the support.The SACs could play the role of the natural enzyme mimics to activate O2,H2O2,etc.,to generate reactive oxygen species.Finally,the SACs were further applied to enzyme-like catalysis therapy,which can kill cancer cells by greatly increasing the level of reactive oxygen species in tumor cells,achieving a good cancer treatment effect.The main contents are as follows:1.Ordered SiO2 channels confined Co1 sites for efficient propane dehydrogenationSiO2 nanomeshes(NMs)with ultrashort three-dimensional(3D)channels were constructed to efficiently immobilize Co single atoms,obtaining Co SAs/SiO2 NMs.Firstly,under the induction of CTAB,TEOS hydrolyzed and self-assembled under alkaline conditions to form SiO2@CTAB composites.Subsequently,carbon in SiO2@CTAB composite was vaporized under an air atmosphere to form ultrashort 3D channels.The carbon removal process resulted in abundant oxygen vacancies in the channel sills,which can immobilize free Co1 species to acquire sinteringresistant Co SAs/SiO2 NMs catalysts.The obtained Co SAs/SiO2 NMs with unsaturated Co-O3 sites exhibited excellent propane dehydrogenation(PDH)performance(selectivity:95%,TOF:196 h-1).Furthermore,the Co SAs/SiO2 NMs showed high stability without obvious inactivation after 24 h of reaction.The Co-O3 sites can selectively activate the first and second C-H bonds and inhibit further C-H(C)bond cleavage during PDH,as demonstrated from theoretical and experimental analysis.2.Biocompatible ruthenium single-atom catalysts for cascade enzyme-like therapyIn this work,we constructed the Ru single atom enzymes(Ru SAEs)with excellent multiple enzymatic activity by anchoring the Ru single atoms on biocompatible carbon dots.Firstly,EDTA was used as ligand to immobilize Ru3+.Then Ru SAEs with Ru-N2C2 active sites and abundant carbon defects were obtained through coordination pyrolysis strategy.Ru SAEs have peroxidase(POD)-,oxidase-and glutathione oxidase-like activities,which can simultaneously catalyze the decomposition of H2O2 to generate·OH,the activation of O2 to O2·-and the oxidation of intracellular reduction agent(glutathione)to increase the level of harmful free radicals in vitro,thereby amplifying free radical damage and ultimately leading to cancer cell death.Subsequently,Ru SAEs were applied to the treatment of tumors in mice based on the outstanding enzyme-like catalytic performance and photothermal effect.The good therapeutic effect was achieved with tumors were completely ablated after only 8 days of treatment.Notably,the POD activity of Ru SAEs exceeded most of SAEs with a specific activity of 7.5 U/mg.Theoretical calculation results showed that Ru-N2C2 in Ru SAEs can efficiently activate H2O2 to generate·OH through a self-splitting mechanism,with an energy barrier of only+0.37 eV.Our work has great implications for the rational design of SAEs for cancer therapy.3.Sulfur atom doping enhances the enzymatic activity of Ni SAE to trigger ferroptosis-based tumor therapyA rising generation nanozyme,single atom enzyme(SAE)has exhibited great potential for cancer therapy,which was contributed to the maximum atom-utilization efficiency and well-defined electronic structures.However,it remains a tremendous challenge to precisely regulate the electronic structure of single atom enzyme.Herein,we developed an anion exchange strategy for precise-controlled the production of a sulfur and nitrogen dual doped Ni SAE.Firstly,NiS nanocubes were obtained by anion exchange of NiCo PBA.Subsequently,NiS@PDA was obtained by coating PDA on NiS.Finally,NiS@PDA was pyrolyzed at high temperature to obtain N,S co-doped carbon-supported Ni SAE.In particular,peroxidase-like activity and glutathione oxidase-like activity of the Ni SAE were significantly enhanced in comparation to simply nitrogen-doped nickel single atom enzyme(Ni SAs/C,N).Thus,sulfur doping can tune the electronic structure of the active center by modulating the metal-support interaction to boost enzyme mimic activity.Moreover,both in vitro and in vivo results demonstrated that PEGylated Ni SAE could efficiently produce oxidized hydroxyl radicals and deplete reduced GSH in tumor microenvironment(TME),resulting in ferroptosis of tumor cells via inducing lipid peroxidation(LPO)and inactivating glutathione peroxidase 4(GPx-4).This study paved an approach to precisely construct polynary heteroatoms-doped single atom enzyme for ferroptosis-based cancer therapy.