Preparation,property Regulation And Application Research Of Multifunctional Co-Based@MnO₂ Nanocomposites

In recent years,the incidence of malignant tumors and the number of deaths increased year by year,has become a threat to human life and health of the number one killer.At the same time,due to the increase in drug resistance and the limitations of monotherapy,traditional cancer treatment methods are difficult to achieve satisfactory results.Due to their unique physical/chemical properties and excellent biosafety,manganese oxide nanomaterials and their derivatives have been widely used in bioimaging,biosensors,drug/gene delivery and tumor therapy.However,despite the significant progress made in manganese oxides and their derivatives,the development of an ideal manganese oxide-mediated nanoplatform that combines multiple therapeutic modalities into a single system to achieve multimodally synergistically enhanced tumor therapy remains a challenge.Based on this,this paper aims to construct a structurally controlled multifunctional manganese oxide composite nanometer platform for the application of Magnetic Resonance（MR）imaging and multimode collaborative therapy in tumor microenvironment response.The main research contents of this paper are as follows:（1）Hollow mesoporous Co₉S₈@MnO₂ intelligent nanometer platform was successfully synthesized by KMnO₄ reduction method.The transformation of Co₉S₈@Mn O₂ core-shell structure to hollow double-shell structure can be realized by regulating reaction time.In addition,the T₁ and T₂ signals of the Co₉S₈@MnO₂ nanomaterials at low pH and hydrogen peroxide solution（pH=5.5/H₂O）were enhanced by 18times and 3 times,respectively,compared to normal tissue fluid（p H=7.4）.Therefore,the Co₉S₈@MnO₂ probe designed by us can be used as a T₁/T₂dual-mode MR contrast agent in response to tumor microenvironment for tumor-specific MR imaging.（2）Based on the hollow bilayers,we further loaded Doxorubicin（DOX）and Indocyanine Green（ICG）to construct a photothermal/photodynamic/chemotherapy multi-mode collaborative tumor treatment platform.The designed Co₉S₈@MnO₂ nanometer platform has superior photothermal conversion efficiency（34.7%）and photothermal stability,and achieves DOX drug release with dual response of pH and near infrared（NIR）.Moreover,the MnO₂-catalyzed reaction based on the tumor microenvironment has solved the hypoxia problem faced by photodynamic therapy,greatly increased the production of reactive oxygen species,and improved the efficacy of photodynamic therapy.The results of tumor treatment showed that the Co₉S₈@MnO₂nanometer platform designed by us can effectively utilize the tumor microenvironment and realize the synergism of multiple modes of photothermal/photodynamic/chemotherapy to increase tumor treatment.Therefore,this study provides an opportunity for the design of a novel multi-functional collaborative self-reinforcing tumor treatment nanometer platform.（3）Co₃O₄ nanocrystellate（～45 nm）was synthesized by thermal decomposition method,and the Co₃O₄@MnO₂ composite nanomaterial was further prepared.The prepared Co₃O₄@MnO₂ nanocomposite has good photothermal conversion efficiency and photothermal stability.In addition,Co₃O₄@MnO₂ not only has excellent magnetic properties,but its T₁ and T₂ signals are enhanced by 20 times and 0.3 times in the presence of low pH and hydrogen peroxide,respectively.Therefore,the synthesized nanomaterials have potential applications in MR imaging and photothermal therapy of tumor microenvironment response.