Nano-platinum(?)-iron(?) Bimetallic Coordination Polymer For Combination Chemotherapy And Chemodynamics Therapy Of Tumors

Cisplatin has therapeutic effects on a variety of tumors,but its clinical application is severely limited by its side effects and drug resistance.The platinum???prodrug overcomes the defects of the platinum?II?drug with its advantages of good stability,good fat solubility and low toxicity.However,platinum???prodrugs are also rapidly eliminated in the kidneys,leading to a reduction in effective therapeutic doses.In addition to chemotherapy,other cancer treatments include photothermal therapy,photodynamic therapy,chemodynamic therapy,and immunotherapy.Among them,chemodynamic therapy uses iron-based nanomaterials to dissociate metal ions under the micro-acidic conditions of the tumor,and through the Fenton or Fenton-like reaction,the excess hydrogen peroxide in the body is decomposed to generate hydroxyl radicals,resulting in apoptosis.Combining platinum???prodrugs with chemodynamic therapy,using hydroxyl radicals produced by chemodynamic and platinum?II?compounds reduced by platinum???to kill tumor cells,while reducing glutathione and hydrogen peroxide levels in the body.The purpose of reducing cisplatin toxic side effects and improving the tumor microenvironment can be achieved.In order to overcome the shortcomings of cisplatin toxic side effects,and enhance the effect of chemodynamics,improve the tumor microenvironment,using cisplatin and hydrogen peroxide as raw materials,terephthalic acid as an axial ligand,the complex Pt???-HBdc₂ was synthesized by oxidation reaction and nucleophilic substituting reaction.Then Pt???-HBdc₂and iron perchlorate were used as raw materials to synthesize nanoplatinum???-iron???bimetallic coordination polymer Pt/Fe-Bdc by solvothermal method.Pt???-HBdc₂ was characterized by NMR,IR and MS.Pt/Fe-Bdc was characterized by SEM,TEM,XRD,BET,Raman and IR.The stability of Pt/Fe-Bdc in different pH environments was determined by spectrophotometry.The effect of cell viability of Pt???-HBdc₂ and Pt/Fe-Bdc were tested by MTT method for multiple cells.The apoptosis of tumor cells induced by Pt/Fe-Bdc was tested by flow cytometry.The ability of Pt/Fe-Bdc to produce ROS was determined by methylene blue degradation method and confocal fluorescence imaging.The levels of glutathione in cells were treated by Pt???-HBdc₂ and Pt/Fe-Bdc were investigated by spectrophotometry.The subcutaneous tumor-bearing mouse model was established using nu/nu nude mice,and the tumor inhibition rate of Pt/Fe-Bdc was studied.The results show that Pt/Fe-Bdc is a regular octahedral nanocrystal with a particle size of 80-110 nm.It can be gradually dissociated under micro-acidic conditions?pH=5.4?,releasing Fe³⁺ions and Pt???-HBdc₂.Among them,Fe³⁺ions can cause hydroxyl radicals to kill tumor cells by Fenton-like reaction,and Pt???-HBdc₂is reduced to cisplatin by glutathione or ascorbic acid in tumor cells,killing tumor cells.Pt???-HBdc₂ and Pt/Fe-Bdc have little effect on normal cells;Pt/Fe-Bdc can induce apoptosis,and with increasing concentration and incubation time,cells are more prone to apoptosis;Pt/Fe-Bdc catalyzes the production of hydroxyl radicals by H₂O₂ in tumor cells,which has certain chemodynamic effects;Pt???-HBdc₂ and Pt/Fe-Bdc can reduce intracellular glutathione content,which in turn improves the tumor microenvironment;Pt/Fe-Bdc can effectively inhibit tumor growth in mice,and has lower side effects than cisplatin.Pt/Fe-Bdc combined with chemotherapeutic and chemodynamic treatment has better anti-tumor effects in vitro and in vivo.In addition,by consuming glutathione and hydrogen peroxide in cells,the tumor microenvironment can be effectively improved and promote apoptosis.Pt/Fe-Bdc has the advantages of low toxic side effects on normal tissues and strong anti-tumor activity,provides a new idea for more effective treatment of tumors.