Experimental Study On Treatment Of Transplanted Liver Tumor With Galactosylated Human Serum Albumin Magnetic Nanoparticles Containing Adriamycin

Objective:Primary hepatocellular carcinoma is one of the most common tumor.Liver is also common site of metastasis of other primary tumor.The mortality rate of the patients with liver maliganant tumor is very high, chemotherapy is an important therapy to treat the liver cancer. Because of improvement of early diagnostic technology , the resection rate of primary hepatocellular carcinoma has improved recently, but the post-operation easily recurred .One of the cause of recurrence are a lot of micro-cancer which was remained after operation.If we can undergo chemotherapy to micro-cancer, Recurrence of post-hepatectomy could be reduced or delayed.The efficacy of conventional system chemotherapy and continuous regional artery perfiision was unsatisfied because the methods can not dimisnish the toxicity of chemotherapeutic drugs to normal cells.In this study, human serum albumin mangnetic nanoparticles which the diameter is 150nm prepared by biophysical methods have excellent targeting effect,and the realease ofchemotherapeutic drugs from this nanoparticles can controlled.In addition, The human serum albumin mangnetic nanoparticles nanoparticles can extravasate the endothelium of the tumor tissue and the included chemotherapeutic drugs was available at cellular and/or subcellular level.Methods: : Galactosyated human serum albumin were prepared by covalent coupling lactose to albumin using reductive amination method. gala-HAS,magnetite and purified adriamycin hydrochloride were mixed by appropriate proportion, and examine the properties of the gala-HS A nanoparticles. Using radioactive tracer technique, Gala-HS A magnetic nanoparticles containing adriamycin and human serum albumin magnetic nanoparticles containing adriamycin were labelled with 125I . 125I human serum albumin magnetic nanoparticles containing adriamycin were injected into hepatic artery, Study on targeting distribution of Gala-HSA magnetic nanoparticles containing adriamycin in normal rats and in transplanted rat liver cancer model.To observe efficey of Gala-HSA magnetic nanoparticles containing adriamycin for Transplanted Liver Cancer in rat.Results: The Gala-HSA magnetic nanoparticles containing adriamycin has obvious hepatic targeting tendency in vivo,In normal rat , uptake quantity Of Gala-HSA magnetic nanoparticles containing adriamycin 2~3 times as high as that of human serum albumin magnetic nanoparticlescontaining adriamycin(control group). In transplanted rat liver cancer model, uptake quantity Of Gala-HSA magnetic nanoparticles containing adriamycin 2.3-3 .5times as high as that of human serum albumin magnetic nanoparticles containing adriamycin(control group).In presence or absence of magnetic field,the target distribution of Gala-HSA magnetic nanoparticles containing adriamycin in normal liver and transplanted liver cancer in rat was observed.The result demonstrated the radioactivity of magnetic field area of liver was 2.7 times as high as non-magnetic field tissue area of liver and the radioactivity of tumor tissue was 7.9 times as high as non-magnetic field area of liver if left lateral lobs of the liver or tumor area was exposed to the magnetic field for 30 minutes.No statistics was found between the target and non-target site of normal liver in rat.However,the radioactivity of tumor tissue was 2.7 times as high as the normal liver tissue. In absence of magnetic field,the rats treated with 0.5mg/kg adriamycin in form of the carrier, Before therapy ,no statistic difference was found in each group volume of tumor in transplanted liver cancer rat (p>0.05).After therapy, statistic difference was found in each group volume of tumor (p<0.05). The results showed that , In absence of magnetic field, the survival time was prolonged in transplanted liver cancer rats treated with Gala-HSA magnetic nanoparticles containing adriamycin treated group, In presence of magnetic field ,the survival time was remarkablely prolonged in rats Gala-HSA magnetic nanoparticlescontaining adriamycin treated group (p<0.01); Histology demonstrated the...