Design And Synthesis Of FePt-based Nanocomposites And Its Application In The Field Of Nanocatalytic Medicine

Nanocatalytic tumor therapy is a treatment method that utilizes the redox ability of nanomaterials under the stimulation of tumor microenvironment,and relies on some chemical components to produce toxic substances to achieve the regulation of cancer cells.Since H₂O₂concentration in tumor cells is much higher than that in normal cells,the Fenton reaction using H₂O₂ as reactant to produce highly toxic hydroxyl radical(·OH)has attracted more and more attention from anti-tumor researchers.The FePt nanomaterial with a face-centered cubic structure(fcc)is a typical Fenton catalyst.Due to its special structural composition,FePt nanomaterials can easily decompose and release a large number of iron and platinum ions under acidic conditions.In addition,the superparamagnetism of FePt materials and their high X-ray absorption capacity lay the foundation for nuclear magnetic resonance(MR)and computed tomography(CT)imaging in vivo.However,due to the easy agglomeration,difficulty of transport and potential biotoxicity of FePt nanoparticles,further transformation applications in organisms have been hindered.In this paper,three multifunctional FePt-based nanocomposite systems were designed by selecting different carrier materials(covalent organic polymers,metal-organic backbones,and nitrogen-doped carbon materials),which used the characteristics of the carriers achieving synergistic effects such as targeting,photothermal,sustained release,and catalysis while ensuring the safe transportation of metal materials,and explored the mechanism and role of materials in catalysis and treatment.(1)FePt-based covalent organic polymers with core-shell structure are used for specific tumor therapyAiming at the fact that the good Fenton catalytic effect of FePt materials and the problems of easy agglomeration and potential biotoxicity are the main contradictions,the 50 nm FePt cube was selected as the core material,and the covalent organic polymer(COP)with porous,rich functional groups and high biosafety was selected as the transport carrier,thereby a FePt@COP-FA nanocomposite(FPCF NCs)with a clear core-shell structure was constructed.Through experiments,it was found that FPCF NCs could remain stable under normal physiological conditions,and under the stimulation of the micro-acid environment,they could catalyze H₂O₂ to produce a large amount of·OH.In addition,FPCF NCs have good photothermal properties,which could be used for synergistic treatment by chemodynamic combined with photothermal therapy.In vitro and in vivo experiments have proved that the FPCF nanocomposites designed by this work can not only achieve the safe transportation of FePt but also achieve effective anti-tumor purposes through combination therapy.(2)The construction of the organic framework of the FePt Fund and its anti-tumor researchFor the problems of easy agglomeration and poor tumor aggregation ability in the water of small-size FePt materials,the FePt nanoparticles with a particle size of 3-5 nm were selected as catalysts,and NH₂-MIL-101(Fe)with high specific surface,easy functionalization and pH response ability were used as the carrier to dope FePt particles in situ in the oil phase.A hybrid FePt-MOF-t Ly P-1 nanocomposite(FPMt NCs)was constructed and its therapeutic effects in vitro and in vivo were studied.Experiments have shown that the frame structure of NH₂-MIL-101(Fe)gradually collapses under slightly acidic conditions,and the FePt particles in it trigger a Fenton catalytic reaction,while didn't occur under normal physiological conditions.At the cellular level,FPMt NCs entered tumor cells through membrane-permeable peptide action and showed high efficiency in inducing apoptosis and ferroptosis.Comparison at the animal level proved the effective tumor inhibition effect of the material.In addition,due to the high magnetization intensity,FPMt NCs was used as MR and CT contrast agents guiding cancer treatment with precise imaging.(3)Dual catalytic function of Fe₂ cluster nanoenzyme induction of ROS accumulation promotes tumor catalytic therapyAiming at the problem of insufficient ROS due to the high redox homeostasis in tumor cells and the low catalytic activity of the traditional Fenton catalyst,we used a porous,high specific surface area,high stability nitrogen-doped carbon material as the carrier,and the metal iron was anchored in situ on the carbon substrate by the limit-pyrolysis method to obtain atomic-level dispersed metal sites,and the small molecule tamoxifen(TAM)was coated to improve the tumor acidity to promote the Fenton reaction.Fe₁ single atom(Fe₁-N-C)and Fe₂diatomic clusters(Fe₂-N-C)were prepared in this system,and it was confirmed that both materials have dual catalytic activity,which could not only catalyze Fenton-like reactions but also consume GSH,and Fe₂-N-C exhibits a better catalytic effect than Fe₁-N-C.Cell experiments have shown that the production of reactive oxygen species could not only lead to apoptosis of tumor cells,but also induce lipid peroxide(LPO)upregulation,triggering iron death in tumor cells,moreover the loss of GSH leads to the inactivation of GPX4 and aggravates iron death.At the same time,the catalytic effect of the material was further enhanced by the accumulation of lactic acid of the TAM and the photothermal conversion performance of the carbon-based material.This study demonstrated through in vitro and in vivo experiments that the diatomic nanoenzyme has a highly effective tumor suppressor effect,which lays the foundation for promoting precise synergistic tumor therapy.