The Role Of NIR Laser-responsive Fe/MOF Based Nanosystem In PDT/PTT Of Breast Cancer

1.Research Background:Breast cancer is the most common female malignant tumor,and its incidence rate and mortality are growing rapidly worldwide.At present,the main treatment methods include surgery,chemotherapy,radiotherapy,endocrine therapy,and targeted therapy,which have problems such as significant trauma,toxic side effects,and drug tolerance.In order to meet the requirements of minimally invasive and precise treatment,researchers have developed some new treatment strategies,such as photodynamic therapy(PDT)and photothermal therapy(PTT),which have been proven to be effective measures for cancer treatment.However,due to the complexity of tumor tissue and the irreversible hypoxia environment,their application in clinical tumor treatment is limited.Up to now,there have many different ways to improve the hypoxia in tumors,such as direct delivery of oxygen,in-situ generation of oxygen and improvement of blood flow.Among them,nano-enzyme is a research hot spot in recent years.It has good stability and biocompatibility,and can carry different drugs for tumor cooperative treatment while improving the tumor microenvironment.2.Purpose and Significance:Based on the above background,we have selected a stable metal-organic framework named Fe-MOF-5(FM5)to prepare composite nano-materials.We prepared a composite nano-material F-I@FM5 using FM5 encapsulated photosensitizer indocyanine green(ICG).The enzyme activity of FM5 is used to promote the decomposition of hydrogen peroxide in the tumor microenvironment and improve the hypoxia of the tumor microenvironment.Then enhancing the Tumor inhibition effect by strengthening the PDT and PTT.3.Research methods,content and process:(1)Preparation and characterization of nanoparticles:After the synthesis of FI@FM5,we studied the characteristics of F-I@FM5 including surface morphology,surface element distribution,size,stability and others.(2)Physical and chemical properties of nano-particles:We used oxygen concentration measurement,infrared camera dynamic monitoring of temperature change,active oxygen indicator and other methods to verify catalase-like activity,photo-thermal conversion performance and photodynamic performance of F-I@FM5.(3)Cell experiment part:We used MTT experiment,flow cytometry,fluorescence staining and other basic methods to study the uptake behavior of cells to nanoparticles,the ability to generate reacti ve oxygen species in cells,the cytotoxicity of nanomaterials and the effect of tumor inhibition at cell level.(4)Animal experiment part:EMT-6 cells were injected subcutaneously into BALB/C nude mice(4 weeks old,15-16 g)to build a tumor model.Materials were injected into the tail vein according to different groups.Then the changes of tumor volume and body weight were recorded for 14 days.After 14 days,the nude mice were killed and the main organs(including heart,liver,lung,spleen,kidney)and tumors were taken for H&E staining to verify the tumor inhibition effect and biological safety.4.Conclusions:In the study we successfully developed the F-I@FM5,a new type of nanocomposite with good stability.After entering tumor cells,it can effectively improve the hypoxia status of tumor,thus promoting the PDT/PTT effect to improve the treatment efficiency of tumor cells.In addition,our nano-materials have biological safety,which will not cause damage to normal organs while effectively treating.The composite nano-material provides an example for the combination of nano-enzyme and optical therapy to improve the effect of tumor treatment,and plays an important role in the exploration of anti-cancer.