Study On The Construction Of Photothermal Enhanced Nanoenzyme Based On Prussian Blue And The Optimization Of Tumor Catalytic Therapy

Nanoenzyme-based catalytic therapy can catalyze the production of reactive oxygen species（ROS）from specific substances only within tumor tissues and cause apoptosis of tumor tissues.However,the complex tumor microenvironment（TME）limits catalytic performance of nanoenzyme,which leads to unsatisfactory therapeutic results..In order to improve the catalytic efficiency of nanozymes,photothermal enhanced nanozymes based on Prussian blue were designed and optimizing tumor catalytic treatment strategies were explored by us.The work of this paper is mainly developed from the following four aspects:In the first chapter,the current status of malignant tumors and traditional therapeutic approaches are introduced.Then,novel tumor therapeutic strategies based on tumor microenvironment-specific response nanoplatforms are reviewed,.Subsequently,the current research status of nanoenzymes and nanocatalytic therapy and the advantages and shortcomings of Prussian blue in tumor therapy are analyzed.Finally,the purpose and significance of constructing nanoenzymes with enhanced photothermal effect are introduced.In the second chapter,functional nanoenzymes Cu/ZIF-67/PB were synthesized by modifying Prussian blue on the surface of Cu²⁺-doped zeolite imidazole framework for GSH consuming and photothermal enhancement of dual enzyme activity.The nanoenzyme with the best catalytic performance in the simulated tumor microenvironment（TME）was selected by modulating the ratio of Cu²⁺.After modifying Prussian blue,the photothermal performance,POD-like activity,CAT-like activity,and photothermal-enhanced dual enzyme activity were investigated.Subsequently,Doxorubicin（DOX）was loaded and the drug release properties were investigated with different p H/GSH conditions.The safety of Cu/ZIF-67/PB/DOX was demonstrated by cellular level experiments,and experiments in mice demonstrated the good therapeutic effect of Cu/ZIF-67/PB/DOX,and the optimization strategy was obtained through GSH consumption,photothermal enhancement of double enzyme activity and chemotherapy synergy.In the third chapter,nanozyme Cu O₂/PB was obtained by combining Cu O₂nanoparticles with Prussian blue nanoparticles for GSH consumption/H₂O₂self-supply while achieving photothermal enhancement of POD-like activity for catalytic therapy.The effect of TME on POD-like activity was obtained by MB degradation experiments under different p H/GSH conditions,and the H₂O₂production mechanism and GSH depletion mechanism of Cu O₂/PB were probed by potassium permanganate colorimetric method and neocuproine.Subsequently,the photothermal properties and photothermally enhanced POD-like activity of Cu O₂/PB nanoenzymes were explored.The specificity of Cu O₂/PB nanoenzymes was confirmed by cellular experiments and the imaging performance of Cu O₂/PB nanoenzymes was verified by magnetic resonance imaging（MRI）experiments.Experiments in mice demonstrated significant anti-tumor effects,and the optimization strategy was obtained through GSH consumption/H₂O₂self-supply and photothermal enhancement of POD-like activity.In the fourth chapter,a series of bimetallic ion-doped Prussian blues were synthesized by modulating the ratio of Co²⁺and La³⁺,and their photothermal properties were tested to select the Prussian blue with the best photothermal properties.The mechanisms of GSH depletion and·OH generation were postulated by XPS.Then MOF-199 with acid-responsive function was wrapped on the Co/La-PB surface and loaded GOx.The photothermal performance and multi-enzyme activity of Co/La-PB@MOF-199 were investigated,and the mechanisms of the stability,GOx release and H₂O₂generation of Co/La-PB@MOF-199/GOx were discussed.The selective cytotoxicity and cascade reaction of H₂O₂-selfsupplied were demonstrated by cellular experiments.Experiments in mice demonstrated satisfactory anti-tumor effects,and the optimization strategy was obtained though GSH consumption/H₂O₂continuous self-supply and photothermal enhanced multi-enzyme cascade reaction.