Preparation And Application Of Adriamycin/Fe₃O₄ Nanoparticles Microspheres To HCC

Purpose:TACE is currently an important treatment for advanced hepatocellular carcinoma.In this study,we prepared Adriamycin/Fe₃O₄nanoparticles microspheres?ADM/Fe₃O₄-MS?which included adriamycin,Fe₃O₄nanoparticles and gelatin.It can produce synergistic anti-tumor effects of tumor arterial embolism,chemotherapy and microwave hyperthermia,and improve the efficacy of tumor embolism treatment.Methods:ADM/Fe₃O₄-MS with controllable particle size were prepared by high-voltage electrospraying method.The particle size of ADM/Fe₃O₄-MS were observed and determined by fluorescent inverted microscope and biological inverted microscope.The loading content and in vitro release behavior was measured by ultraviolet spectrophotometer and ICP-MS.Study the in vitro heat production of ADM/Fe₃O₄-MS with microwave.VSM determinate the hysteresis curve of ADM/Fe₃O₄-MS.ADM/Fe₃O₄-MS with microwave hyperthermia were studied by MTT assay and Annexin V-PI double staining method in antitumor effect.VX 2 tumor rabbits were used as model animals to investigate the tumor-inhibitory effect of ADM/Fe₃O₄-MS combined with microwave thermotherapy in vivo.Results:The optimized conditions for preparing ADM/Fe₃O₄-MS by high-voltage electrospraying method were that gelatin solution concentration was 2%,glutaraldehyde solution concentration was 1%,using a 27G needle,the flow rate was 3m L/h,the voltage was 20KV and the dosing ratio of adriamycin was 5%.The average particle size of ADM/Fe₃O₄-MS was 217.7±57.4?m,the loading content of adriamycin was 1.7±0.1%,and the loading content of Fe₃O₄nanoparticles was 4.9±0.6%.Adriamycin of ADM/Fe₃O₄-MS can be continuously released for more than 26 days.Meanwhile,ADM/Fe₃O₄-MS have superparamagnetism and a good imaging effect in MRI.With microwave,ADM/Fe₃O₄-MS can rapidly increase temperature of water and maintain for a long time.Using VX 2 cells as model cells,the cell vitality of ADM/Fe₃O₄-MS group was 37.3±10.6%.After microwave,the efficacy of anti-tumor cells of ADM/Fe₃O₄-MS was further improved,and the cell vitality was only 12.0±2.0%.In addition,Annexin V-PI double staining method confirmed that ADM/Fe₃O₄-MS combined with microwave hyperthermia had the most significant apoptosis and necrosis.In vivo studies have shown that ADM/Fe₃O₄-MS can effectively occlude arteries of tumor rabbits,and the microspheres combined with microwave thermotherapy can significantly inhibit tumor growth.Conclusion:The above results show that ADM/Fe₃O₄-MS with controlled particle size can be successfully prepared by high-voltage electrospraying.The microspheres can effectively carry adriamycin and Fe₃O₄nanoparticles.ADM/Fe₃O₄-MS can slowly release adriamycin and have a good imaging effect in MRI.At the same time,with microwave hyperthermia,the anti-tumor efficacy of ADM/Fe₃O₄-MS can be further improved.It is expected to be used in the embol-chemo-thermo combinational treatment of hepatocellular carcinoma.