Study On The Hydrogen Peroxide Sensing And Chemodynamic Therapy For Cancer Of Carbon Dots-Layered Double Hydroxides Composite

Tumor microenvironment（TME）has hypoxia,weak acidity and excessive H₂O₂.Among them,H₂O₂ is connected to the proliferation,metastasis and apoptotic of cancer cells.Therefore,H₂O₂ is an effective molecular biomarker for early diagnosis of cancer.In addition to early detection,a number of therapeutic strategies have been developed for cancer,such as chemotherapy,photodynamic therapy（PDT）,radiotherapy（RT）,photothermal therapy（PTT）,and chemodynamic therapy（CDT）.Among them,CDT relies on tumor cells to produce·OH to kill cancer cells by Fenton/Fenton-like reaction with H₂O₂under acidic conditions,thus inhibiting tumor growth.In view of the important role of H₂O₂ in tumor theranostics,the development of a nano-diagnosis and treatment platform with both H₂O₂ detection and enhanced CDT performance is of great significance for early diagnosis and collaborative treatment of tumors.Scientists mostly assemble materials with different functions into multi-functional nanoplatforms to achieve the purpose of sensing to different objects and collaborative treatment,but it is still a challenge to realize the enhancement of sensing and therapeutic functions through the interaction of materials.As a two-dimensional layered nanomaterial,layered double hydroxides（LDHs）has the peculiarities of tunable main laminate elements,strong drug loading ability and good biocompatibility,and is an excellent carrier for constructing multifunctional composite materials.In combination with the characteristics of low toxicity and strong stability of fluorescent carbon dots（CDs）,which can be used for biological imaging,this paper constructed two kinds of composite nanomaterials by loading negatively charged fluorescent CDs on LDHs.Through the charge transfer between CDs and LDHs,the H₂O₂fluorescence sensing performance that CDs alone cannot achieve was innovated,and the CDT treatment ability of LDHs was strengthened.The fluorescence recovery mechanism of H₂O₂ specific response under charge transfer mechanism and the mechanism of Fenton reaction rate increase were revealed.It provides a new way and theoretical foundation for the design and performance enhancement of materials for early diagnosis and collaborative treatment of cancer.The specific research contents of this paper are as follows:1.The research on the construction of CDs/CuAl-LDH and its H₂O₂detection/CDT performance.Ultrathin CuAl-LDH was prepared by“bottom-up”synthesis method and loaded with fluorescent CDs to construct CDs/CuAl-LDH nanocomposites,which with excellent H₂O₂ fluorescence sensing imaging and CDT therapeutic properties.CDs induces fluorescence quenching through electron transfer with LDHs layer Cu²⁺,and changes Cu（Ⅱ）to Cu（Ⅰ）,which is more favorable for Fenton-like reaction.CDs/CuAl-LDH showed excellent fluorescence sensing performance for H₂O₂（detection limit:0.37μM）.In addition,due to the generation of Cu（Ⅰ）,the CDT performance of CDs/CuAl-LDH was significantly enhanced compared with that of CuAl-LDH.The V_max of CDs/CuAl-LDH is1.702×10^-7 M^-1 s^-1 at p H 6.5.which is significantly stronger than CuAl-LDH(4.446×10^-8 M^-1 s^-1).In vitro cell experiments also showed that CDs/CuAl-LDH had excellent performance in H₂O₂ fluorescence sensing imaging and CDT treatment.2.The CDs/CoFe-LDH for the study of CDT/PTT synergistic therapy.By utilizing the tunability of metal elements of the main layer of LDHs,Co²⁺and Fe³⁺were introduced to prepared CoFe-LDH.Then,the fluorescent CDs were loaded on the surface of CoFe-LDH by electrostatic adsorption to obtain CDs/CoFe-LDH,which was used for tumor micro-acid environment responsive CDT/PTT synergistic therapy and H₂O₂ imaging.Since electron transfer between CDs and CoFe-LDH induces fluorescence quenching and H₂O₂-stimulated fluorescence recovery,CDs/CoFe-LDH showed good H₂O₂-stimulated fluorescence response properties,providing a basis for tumor-specific fluorescence imaging.Due to the excellent CDT performance of Co²⁺and Fe²⁺,CDs/CoFe-LDH can catalyze H₂O₂ to produce OH in TME.Meanwhile,the composite exhibited good photothermal properties in the NIR region,with a temperature rise of 23.3℃under 808 nm(1.0 W cm^-2)laser irradiation.The results showed that the CDT properties of the composite materials are significantly enhanced under photothermal promotion.Therefore,CDs/CoFe-LDH has unique TME responsive fluorescence imaging and CDT/PTT synergistic therapeutic properties,providing a new strategy for the construction of multifunctional nanoplatforms.In summary,based on the mechanism of charge transfer between materials,this paper synthesized nanocomposites with H₂O₂ fluorescence sensing imaging and enhanced CDT therapeutic performance by utilizing lamellar element tunability of LDHs and fluorescence characteristics of CDs,providing a new idea for the field of tumor early diagnosis and collaborative therapy.