Construction Of Folic Acid And (3-carboxypropyl) Triphenyl Phosphine Bromide Modified Nanomaterials And Targeted Therapy For Tumor

Background: The mortality rate of cervical cancer ranks fourth among female malignant tumors in the world at present,and the recurrence rate of patients with cervical cancer is about 28% to 64%,which has become a major killer endangering women’s health.There are a variety of traditional treatments for cancer,mainly surgery,chemotherapy,radiotherapy and so on.These traditional treatments have high recurrence rate,great side effects and great harm to the body,so there is an urgent need to study new treatments and drugs.In recent years,with the development of nanotechnology,the anti-tumor effect of nanomaterials in the field of biomedicine has been excavated.Nanomaterials have become a new alternative to tumor therapy because of their strong stability,high safety,large specific surface area and easy modification.Because of the special physiological structure of cancer cells,such as large vascular endothelial space and no lymphatic reflux,nano-sized particles can enter the tumor microenvironment and cancer cells,and can accumulate in large quantities in the tumor.This passive targeting ability is called the permeability and retention effect of nanomaterials(EPR effect).Under the irradiation of near-infrared light,nanomaterials can produce high fever and kill tumor cells by thermal ablation,which is called photothermal therapy;under the irradiation of near-infrared light,the transition of electrons occurs and reactive oxygen species(ROS)are produced,which play a therapeutic role in tumor cells,which is called photodynamic therapy.Based on the EPR effect,photothermal effect and photodynamic effect of nanomaterials,nanomaterials can kill tumor cells at low concentrations and damage normal tissues less,which provides a feasible idea for the treatment of cervical cancer cells.Objective: 1.Ag3PO4/Mxene nanomaterials were prepared and modified to enhance the water solubility and targeting ability of nanomaterials.To study the properties,biocompatibility,targeting ability and inhibitory effect of the synthesized composite nanomaterials on cervical cancer cells in vitro and transplanted tumor in vivo.Methods: 1.25%Ag3PO4/Mxene nanomaterials were prepared by coprecipitation method.2.PEG,FA and TPP were loaded on Ag3PO4/Mxene nanomaterials by chemical synthesis and electrostatic adsorption.3.The nanometer materials were characterized by TEM,SEM,FT-IR,XPS,XRD,PL,DRS,UPS and so on.4.The nanomaterials were irradiated with 808 nm nearinfrared light to detect their Calories and reactive oxygen species(ROS).5.The safety of nanomaterials was detected by MTT test,hemolysis test,Calcein-AM/PI staining of living dead cells,weight detection of animal experiments and HE staining of important organs.6.Scratch test,MTT test and Calcein-AM/PI staining were used to detect the phototoxicity of nanomaterials on cervical cancer SIHA cells in vitro.7.The apoptosis induced by nanomaterials was detected by flow cytometry.8.Mitochondrial probe was used to detect the ability of nanomaterials to target SIHA cells.9.Reactive oxygen species(ROS)probe was used to detect Ros produced in SIHA cells.10.The tumor model in vivo was constructed,and the light-triggered tumor ablation was detected in the tumorbearing mouse model.Results: 1.The characterization of nanomaterials proved that 25% Ag3PO4/Mxene nanomaterials were successfully fabricated.2.FT-IR and SEM scanning electron microscopy showed that PEG,FA and TPP were loaded successfully.3.The temperature of the composite nanomaterials irradiated by near-infrared light reached 53 ℃.4.The composite nanomaterials can target the mitochondria of SIHA cells and produce a large amount of ROS in SIHA cells after near-infrared irradiation.5.The survival rate of SIHA and HUVEC cells treated with composite nanomaterials for 12 hours is more than 95%,which has high biological safety.6.The composite nanomaterials inhibited the proliferation of SIHA cells and the survival rate was 38%.7.The composite nanomaterials can inhibit the growth of SIHA cells in a dose-dependent manner.8.Composite nanomaterials can induce apoptosis of SIHA cells.9.In vivo experiments showed that the composite nanomaterials could reduce the tumor volume of tumorbearing mice.Conclusion:1.The successfully synthesized and modified Ag3PO4/MxeneePEG-FA-TPP nanomaterials can produce high heat and reactive oxygen species(ROS)after near-infrared irradiation,which has good biosafety.2.Composite nanomaterials can target the mitochondria of cervical cancer cells,produce strong phototoxicity,reduce the proliferation of cervical cancer cells and induce apoptosis.3.Composite nanomaterials can inhibit the growth of tumor cells in vivo and reduce the tumor volume of tumor-bearing mice.