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CN-121971607-A - Nanometer enzyme sound sensitizer Co3O4@PAO@BSA (CPB) and preparation method and application thereof

CN121971607ACN 121971607 ACN121971607 ACN 121971607ACN-121971607-A

Abstract

The invention relates to the field of medical materials, in particular to a nano-enzyme sound sensitizer Co 3 O 4 @PAO@BSA (CPB) and a preparation method and application thereof. According to the invention, through synthesizing and regulating the Co 3 O 4 @PAO@BSA (CPB) nano-sonosensitizer, the US enhanced enzyme kinetic strategy with Co 3 O 4 CPHs as a substrate is adopted, the introduction of PAO consumes polyamine in tumors, and the carbonyl stress strategy consumed by the polyamine successfully overcomes the defect of oxidative damage treatment, and the effect of Co ion-mediated SDT/CDT induced oxidative damage treatment is enhanced through the nano-enzyme cascade catalytic effect.

Inventors

  • Jing Xiangxiang
  • SUN DANDAN
  • WEI ZHIHONG
  • LIU MENGYAO
  • WANG XUEHUI
  • ZHANG MIN
  • CUI YANHUA

Assignees

  • 山西省人民医院

Dates

Publication Date
20260505
Application Date
20260212

Claims (10)

  1. 1. The preparation method of the nano-enzyme sound sensitizer Co 3 O 4 @PAO@BSA (CPB) is characterized by comprising the following steps: Step 1, preparing Co 3 O 4 CPHs; Step 2, loading PAO, and preparing and obtaining Co 3 O 4 @PAO; And 3, modifying the Co 3 O 4 @PAO prepared in the step 2 by BSA to prepare the nano-enzyme sound sensitizer Co 3 O 4 @PAO@BSA (CPB).
  2. 2. The method of manufacturing as claimed in claim 1, comprising the steps of: step 1-1, preparing Co-MOFs, namely mixing a cobalt nitrate hexahydrate aqueous solution with a 2-methylimidazole aqueous solution, stirring for 6 hours at 25+/-5 ℃, centrifugally collecting purple precipitate, washing with ethanol, drying, and collecting a purple solid product, namely the Co-MOFs; And step 1-2, preparing Co 3 O 4 CPHs, namely calcining the Co-MOFs prepared in the step 1-1, and collecting a black product, namely Co 3 O 4 CPHs.
  3. 3. The preparation method according to claim 1 or 2, wherein step 2 comprises mixing the PAO with the Co 3 O 4 CPHs, stirring at 25+ -5deg.C for 12h, centrifuging to remove excessive PAO, and collecting black precipitate to obtain Co 3 O 4 @PAO.
  4. 4. The method according to any one of claims 1 to 3, wherein in step 3, BSA is mixed with the Co 3 O 4 @PAO prepared in step 2, stirred, centrifuged to remove supernatant, and the solid is collected to obtain the nano-enzyme sound sensitizer Co 3 O 4 @PAO@BSA (CPB).
  5. 5. The method according to any one of claims 2 to 4, wherein in step 1-1, the molar ratio of cobalt nitrate hexahydrate in the aqueous cobalt nitrate hexahydrate to 2-methylimidazole in the aqueous 2-methylimidazole solution is 1.56:67.2; Preferably, the concentration of the cobalt nitrate hexahydrate aqueous solution is 0.52M, and the concentration of the 2-methylimidazole aqueous solution is 3.36M; preferably, the volume ratio of the cobalt nitrate hexahydrate aqueous solution to the 2-methylimidazole aqueous solution is 3:20.
  6. 6. The method according to any one of claims 2 to 5, wherein in step 1-1, the number of times of washing with ethanol is at least 1, preferably the number of times of washing with ethanol is 3; the drying is 80 ℃ drying for 24 hours.
  7. 7. The method according to any one of claims 2 to 6, wherein in step 1-2, the calcination is 300 ℃ calcination for 3 hours.
  8. 8. The method of any one of claims 1 to 7, wherein in step 2, the mass ratio of PAO to Co 3 O 4 CPHs is 1:1; Preferably, the centrifugation is 8000rpm for 10min, Preferably, in step 3, the mass ratio of the BSA to the Co 3 O 4 @PAO is 2:1.
  9. 9. The nanoenzyme sound sensitizer Co 3 O 4 @ pao@bsa (CPB) prepared by the preparation method according to any one of claims 1 to 8.
  10. 10. Use of the nanoenzyme sound-sensitive agent Co 3 O 4 @ pao @ bsa (CPB) according to claim 9 in any one or more of the following: (I) Preferably, the enzyme comprises one or more of an oxidase-like, peroxidase-like, catalase-like or glutathione peroxidase; (II) decreasing cell membrane stability; (III) preparing a medicament or formulation for reducing oxidative damage in treatment; (IV) preparing a medicament for photodynamic therapy/photodynamic therapy co-treatment; (V) preparing a medicament for treating malignant tumor; Preferably, the nano enzyme sound sensitizer Co 3 O 4 @PAO@BSA (CPB) reverses the anoxic microenvironment, consumes endogenous glutathione and ROS output or promotes the valence state conversion process of Co ions under the excitation of ultrasonic exogenous, increases the generation of ROS and kills tumor cells.

Description

Nanometer enzyme sound sensitizer Co 3O4 @PAO@BSA (CPB) and preparation method and application thereof Technical Field The invention relates to the field of medical materials, in particular to a nano-enzyme sound sensitizer Co 3O4 @PAO@BSA (CPB) and a preparation method and application thereof. Background Prostate, lung and colorectal cancers account for almost half (49%) of all cases of disease in men. For women, breast cancer, lung cancer and colorectal cancer account for 52% of all new diagnoses, with breast cancer alone accounting for 31% of female cancers, the first. Traditional methods of breast cancer treatment include surgery, chemotherapy, radiation therapy, and the like. The operation is wounded, and chemotherapy and radiotherapy lack high specificity, can not avoid producing serious toxic and side effect and drug resistance when treating tumor, very influence the treatment effect. Although immunotherapy and targeted therapy for breast cancer have achieved a certain effect in clinic in recent years, for some special types of breast cancer, such as triple negative breast cancer, the treatment effect is poor, the overall survival rate is low, early recurrence is easy, distant metastasis of lung, brain and the like occurs, and the death rate is still high because of insensitivity to conventional endocrine and targeted therapy and obvious drug resistance. In view of this, development of a novel and efficient treatment method, mode and strategy is still needed at present, and it is expected that not only can efficient treatment of malignant tumors such as breast cancer be realized, but also high treatment safety is achieved, and the life cycle and life quality of patients can be ensured. In recent years, the development of ultrasonic diagnosis and treatment technology provides a wider space for the progress of modern medicine. The tumor kinetic therapy has the advantages of high treatment efficiency, low toxic and side effects, strong controllability and the like, and becomes a hot spot direction of clinical and basic research. Unlike a novel tumor oxidative damage treatment technique based on a tumor endogenous chemical product conversion reaction (Fenton reaction: H 2O2 is catalyzed into toxic OH through mediation of Fe 2+), the dynamic therapy (chemodynamic therapy, CDT) also comprises the steps of exciting active substances by using external fields to generate active oxygen free radicals (Reactive Oxygen Species, ROS) with cytotoxicity to kill tumor cells. Because the generation of ROS is limited to the excitation range of an external field, the influence and damage to normal tissues and cells are smaller, and the toxic and side effects are lower. Currently, such external field-based oncologic therapies are mainly divided into two main categories, one photodynamic therapy under light excitation (Photodynamic therapy, PDT) and the other sonodynamic therapy under ultrasound excitation (Sonodynamic therapy, SDT). In recent years, research on PDT has been greatly advanced and successfully applied to clinical treatment of partial tumors, but it is difficult to perform effective treatment on tumors of deep organs and tissues due to low tissue penetration depth of light. Ultrasound has the advantages of no wound, no radiation, deep tissue penetrability and the like, and becomes a new excitation source for tumor kinetic therapy. SDT is an emerging treatment for oxidative damage, which mainly includes ROS-induced lipid peroxidation of cell membranes (LPO) and DNA damage. Unlike traditional high-intensity focused ultrasound for treating tumor by using thermal effect, SDT adopts low-intensity ultrasound as excitation source, which has penetration depth of more than ten cm in soft tissue, and can be more efficiently focused on tumor tissue to implement kinetic treatment. Has higher therapeutic safety, and has wider application field and clinical transformation prospect compared with PDT. The tumor microenvironment (Tumor microenvironment, TME) refers to the internal environment through which the tumor grows. Tumor cells can promote tumor growth and development by changing and maintaining conditions for their own survival and development through autocrine and paracrine. TME has the characteristics of relatively high concentration of hydrogen peroxide (H 2O2), slightly acidic pH, hypoxia, over-expression of intracellular Glutathione (GSH) and the like. Treatment of tumors by using complex microstructure of tumor tissue and TME has been a focus of research at home and abroad. Reactive Oxygen Species (ROS) are the cellular components of TME produced by tumor cells and are typical TME species that control tumor cell fate, including hydroxyl radicals (.oh), singlet oxygen (1O2), and superoxide anions (.o 2-), among others. The physiological effects of ROS are closely related to their concentration. The ROS with high concentration can damage cell membranes, inhibit mitochondrial functions, damage DNA to cause gene mu