Doxorubicin-Loaded Cu-doped Metal-Organic Framework Nanoparticles For Driving Synergetic Chemo-Chemodynamic Anticancer Therapy

Objectives:In order to successfully deliver chemotherapy drugs to tumor tissue while avoiding or reducing damage to normal tissue,we introduce a copper-based metal-organic framework(CuMOF)as a carrier for the chemotherapy,drug doxorubicin(DOX)to study the synergistic antitumor effect and mechanism of chemokinetic therapy based on copper-based metal-organic framework(Cu-MOF)combined with doxorubicin(DOX).Methods:1.Naoscale Cu-MOF was prepared by a simple stirring synthesis method,and it was stirred with DOX again,so that DOX was loaded in it.The synthesized products were characterized by X-ray Diffraction(XRD);transmission electron microscope,Fourier transform infrared spectrometer and UV-visible absorption spectrometer.2.Observe the loading of drug-loaded nanomaterials and their release in different pH buffers.The purpose of using different pH buffers is to simulate the normal tissue environment and slightly acidic tumor environment.3.The toxicity,targeting and mechanism of action of drug-loaded nanomaterials were verified in vitro.The killing effect of Cu-MOF@DOX on oral cancer cells was detected by CCK8 method,Calcein-AM/PI live dead cell staining method and cell scratch test.and the uptake of nanoparticles and the generation of intracellular ROS by oral cancer cells were observed by laser confocal microscopy.Glutathione(GSH)consumption in cancer cells was detected by glutathione kit,,and the expression of apoptotic proteins BAX and Bcl-2 was detected by Western blot.Results:1.The prepared Cu-MOF and Cu-MOF@DOX nanoparticles are spherical in structure,with regular shape and uniform dispersion.XRD,FT-IR,and UV spectra verified the effective loading of DOX in Cu-MOF@DOX nanoparticles.2.In the drug release experiment of Cu-MOF@DOX,we found that when pH=5.4,the total amount of DOX released at the same time point was significantly higher than the total amount of DOX released when pH=7.4,indicating that Cu-MOF@DOX can be released well in acidic environment.3.Cu-MOF@DOX can kill about 50%of oral cancer cells at a lower concentration(DOX concentration of 1μg/mL).Compared with DOX,DOX in Cu-MOF@DOX is taken up by cells more,and can generate a large amount of ROS in cells,Cu-MOF@DOX can consume GSH,combined with released DOX,and synergistically induce more apoptosis.Conclusions:In this experiment,Cu-MOF@DOX nanoparticles were successfully prepared,and the targeted delivery of chemotherapy drug DOX was realized.The Cu-MOF@DOX has good antitumor properties,and it can selectively enter tumor cells,so that its killing effect on tumor cells is significantly improved.Cu-MOF@DOX promotes the apoptosis of oral cancer cells maint,through the synergistic effect of chemokinetic therapy and chemotherapy.Cu-MOF@DOX has a good application prospect in the treatment of oral cancer.