Preparation And Application Research In Cancer Treatment Of Magnetic Graphene Oxide-based Nano-drug Carriers

Objective:As one of the most common means of cancer treatment,chemotherapy has disadvantages such as poor tumor targeting,serious therapeutic side effects,poor monotherapy effect,and high tumor recurrence and metastasis rate.In recent years,graphene oxide(GO)has been widely used in targeted drug delivery and photothermal therapy.However,GO tends to accumulate in the physiological environment and its passive targeting is not sufficient to enable high concentrations of nanomachine carriers to accumulate in tumor tissues.Therefore,we constructed two novel magnetic graphene oxide(MGO)based nano-drug carriers by functionalized MGO with triformylcholic acid(TCA),folic acid(FA)and maltodextrin polymer(MDP)for targeted delivery of anticancer drugs and synergistic chemo-photothermal therapy,reducing the side effects of drug treatment and improve the effect of cancer treatment.Methods:We synthesized MGO by chemical co-precipitation method,and prepared folic acid grafted maltodextrin polymer functionalized MGO(MGO-MDP-FA)and triformylcholic acid and folic acid functionalized MGO(MGO-TCA-FA)by amide reaction.Transmission electron microscopy,X-ray diffraction,thermogravimetric analysis,Fourier transform infrared spectroscopy and magnetic properties analysis were used to characterize the structure and morphology of the two nano-drug carriers.The photothermal effect of them was evaluated by infrared thermal imager.Nano drug-carrier complexes MGO-MDP-FA@DOX and MGO-TCA-FA@DOX were synthesized by loading the anticancer drug doxorubicin(DOX)on MGO-MDP-FA and MGO-TCA-FA,respectively.And the drug loading and release properties of them were studied by fluorescence spectroscopy.The possible mechanism of drug adsorption was explored through drug loading kinetics and isothermal adsorption.The blood compatibility in vitro was evaluated by hemolysis test.The targeting performance of MGO-MDP-FA@DOX to cancer cells and the targeting ability of MGO-TCA-FA@DOX to liver cancer cells were analyzed by fluorescence imaging.The cytotoxicity of MGO-MDP-FA@DOX and MGO-TCA-FA@DOX was evaluated by CCK-8 cytotoxicity assay and apoptosis and necrosis staining assay.The inhibitory effect of MGO-TCA-FA@DOX on liver cancer in vivo was evaluated by animal experiments.Results:1.The nano-drug carrier MGO-MDP-FA was successfully synthesized with excellent superparamagnetism and photothermal conversion performance.MGO-MDPFA mainly loaded the anticancer drug DOX through chemisorption,with a maximum loading capacity of 657.9 mg/g,and had controllable release properties of near infrared(NIR)responsiveness,the drug release amount of MGO-MDP-FA@DOX under NIR irradiation was 1.84 times higher than that of the condition without NIR irradiation.In vitro studies showed that MGO-MDP-FA@DOX had good blood compatibility,cytocompatibility and targeting of cancer cells.And the cancer cell killing rate of MGOMDP-FA@DOX under NIR reached to 80%,which was significantly better than that of single chemotherapy group(MGO-MDP-FA@DOX)and photothermal therapy group(MGO-MDP-FA+NIR).2.The nano-drug carrier MGO-TCA-FA was successfully synthesized,which has good superparamagnetism and excellent photothermal conversion performance.Drug loading experiments showed that the loading effect of DOX on MGO-TCA-FA was mainly chemisorption,and the drug loading reached 1040 mg/g,as the initial concentration of DOX was 0.4 mg/m L.Drug releasing experiments showed that MGOTCA-FA@DOX had p H and NIR responsive controllable release properties,the drug release rate of p H 5.3 was 27.46% higher than that of p H 7.4 at 40 ℃.And under the same conditions,the release rate increased by 10.9% under NIR irradiation.In vitro and in vivo experiments showed that MGO-TCA-FA@DOX had good biocompatibility and targeting of liver cancer cells,and it possessed a high killing rate of liver cancer cells under NIR.The inhibition rate of liver cancer in vivo of MGO-TCA-FA@DOX+NIR group up to 85%,which was significantly better than the single chemotherapy group(MGO-TCA-FA@DOX)and photothermal therapy group(MGO-TCA-FA+NIR).Conclusion:1.The MGO-MDP-FA nano-drug carrier was successfully synthesized with high drug loading,excellent photothermal conversion performance,good biocompatibility and NIR responsive drug release performance.It could combine passive targeting and active cancer cell targeting of FA to achieve double targeted delivery of anticancer drug DOX.The cancer inhibition effect of chemotherapy combined with photothermal therapy was obviously better than that of single treatment mode.Therefore,MGO-MDP-FA@DOX has potential application value in the treatment of cancer.2.The nano-drug carrier MGO-TCA-FA synthesized in this study had the advantages of good biocompatibility,high drug loading,high photothermal conversion efficiency and p H and NIR responsive controllable drug release performance.It could cooperate with liver cell targeting of TCA,cancer cell targeting of FA and passive targeting to achieve multiple targeted delivery of the anticancer drug DOX.MGO-TCAFA@DOX has a good application prospect in the treatment of liver cancer with chemotherapy and photothermotherapy.