| PART Ⅰ:Preparation and physical characterization description of p(N-isopropylacrylamide-co-acrylic Acid)modified gold nanoparticles Objective:To preparep(N-isopropylacrylamide-co-acrylic Acid)modified gold nanoparticles and describe its physical characterization.Materials and Methods:To compose and characterize the complex of the gold nanoparticles and temperature-sensitive polymers(including GNP@PNIPAM&GNP@PNIPAM-tBA),X-ray attenuation and biocompatibility were measured,and the viscosity,fluidity and phase transition were analyzedResults:The GNP@PNA has a nice viscosity,dispersibility and liquidity characteristics,they are easy for microcatheter injection.Conclusion:GNP@PNA has a good fluidity,effective embolization and high biocompatibility.GNP@PNA can be used as a novel liquid embolization agent.PART Ⅱ:An experimental study on the embolization in rabbit renal arteries with p(N-isopropylacrylamide-co-acrylic Acid)Modified Gold NanoparticlesObjective:To explore the feasibility,safety and persistence of p(N-isopropylacrylamide-co-acrylic Acid)modified gold nanoparticles for embolization in rabbit renal arteryMaterials and Methods:Renal artery embolization of GNP@PNA was performed on normal rabbit(the left kidney of New Zealand rabbit).Review times were set at the point of 1 week,1 month and 2 months,multiphase CT enhancement scans was used to evaluate the recanalization and autoradiography.The pathological examination was uesd to evaluate its durability and long-term efficacy of embolization.Results:The GNP@PNA can embolize the peripheral arteries of the renal arteries,with good dispersibility,excellent embolization effect and high resolution in angiography in the end of the follow-up period(two months).Conclusion:GNP@PNA has a good fluidity,effective embolization and high biocompatibility.GNP@PNA can be used as a novel liquid embolization agent.PART Ⅲ:An experimental study on the embolization in rabbit VX2 liver tumors with p(N-isopropylacrylamide-co-acrylic Acid)modified gold nanoparticles Objective:To observe the effect of embolization and autoradiography of GNP@PNA and evaluate the anti-tumor effectMaterials and Methods:Forty rabbit models of VX2 tumor were established and confirmed by CT.They were randomly divided into four groups.After hepatic arteriography through super-selective catheterization with a 2.7-F microcatheter for determining the location of tumor tissues and their blood-vessels,the rabbits were treated as follows:group A(n = 10):group A were injected with normal saline;group B(n=10):group B were received polyvinyl alcohol(PVA)particles(350-560μm);group C(n=10):group C were treated with Lipiodol/Gelfoam particles(350-560μm);group D(n=10):group D were injected with 0.4ml GNP@PNA.The tumor size,tumor volume and tumor growth rate were observed before and after operation by dynamic contrast-enhanced CT scan.The tumor size and tumor growth rate were observed on the 7th day after operation.The liver and kidney function were measured on the 3rd day and 7th day after operation in order to evaluated the safety of GNP@PNA.Ten rabbits in each group were sacrificed at 7th day after operation.The tumor specimens and the histopathological(HE and Masson stainings)were taken to observe the gross morphology and pathological changes of tumor tissue.The blood samples,heart,liver,kidney,spleen,lung,brain and some tumor tissues of GNP@PNA group were collected and analyzed by vivo distribution and transmission electron microscopy to evaluate its embolization and its high resolution in angiographyResults:GNP@PNA not only can be injected into the tumor through the catheter,but also can embolize the tumor blood vessels and their nutritional artery,at the same time showing its high resolution in angiography.There was no significant difference in the volume of tumors at 0 day before operation(P>0.05).There were significant differences in tumor volume between NS,PVA,Lipiodol/Gelfoam and GNP@PNA at 7 days after operation(7days after surgery P<0.05).Compared with Lipiodol/Gelfoam group,GNP@PNA group showed its high resolution in angiography and expanded its tumor necrosis after embolization.Compared with NS group and PVA group,the GNP@PNA group had a wider range of embolization,higher tumor necrosis rate and high resolution in angiography.Liver and kidney function data showed that it was only a transient liver injury,suggested its high safety,which was no effect on rabbit kidney function.Conclusion:GNP@PNA has a good fluidity,effective embolization,high resolution in angiography and high biocompatibility.GNP@PNA can be used as a novel liquid embolization agent and can inhibit the growth of liver cancer. |
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