乳糖化修饰纳米基因载体治疗肝癌的前期研究
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摘要
目的:制备具有半乳糖基和稳定磁性,能够携带化疗药物的半乳糖白蛋白磁性阿霉素纳米粒,并对半乳糖白蛋白磁性纳米粒的糖化比率、磁性及药物含量进行检测。
方法:将乳糖和白蛋白用还原胺法合成半乳糖基人血白蛋白(galactosylated human serum albumin Gal-HSA);采用滴定水解法制备直径在70nm左右Fe_3O_4磁性纳米粒。将半乳糖白蛋白、Fe_3O_4磁性纳米粒及纯盐酸阿霉素按一定的比率混合,通过在精制棉子油中超声乳化、加热固化变性、乙醚洗涤等工艺制备出半乳糖白蛋白磁性阿霉素纳米粒;用苯酚—硫酸比色法测定半乳糖白蛋白的糖化比率;用乙醇提取法提取半乳糖白蛋白磁性阿霉素纳米粒中的阿霉素,并用液相色谱仪测定其含量。将纳米粒溶于生理盐水中,并在光学显微镜下观察在磁场的作用下,半乳糖基磁性纳米粒的运动情况,用激光粒度分析仪、原子力显微镜和透射电子显微镜观察纳米粒粒径的大小和内部结构。
结果:半乳糖白蛋白磁性阿霉素纳米粒的糖化比率为32;Fe_3O_4纳米粒径在70±30nm左右,粒径均匀;阿霉素的含量为58.45ug/g,阿霉素的包含率为97.53%;半乳糖白蛋白磁性阿霉素纳米粒溶液在光学显微镜下观察,在磁场的作用下,纳米粒迅速向磁铁的方向移动并发生聚集,当磁铁与纳米粒的距离加大时,纳米粒运动速度减慢,并沿磁力线的方向成串珠状聚集。透射电子显微镜下观察Fe_3O_4颗粒均匀分布在半乳糖白蛋白磁性阿霉素纳米粒中。
结论:半乳糖白蛋白磁性阿霉素磁性纳米粒具有较高糖化比率,稳定的磁性,靶向性强,药物包含率高,释药速率可控制的特点,为靶向药物治疗,提供了可靠的载药工具。
Objective:To prepare the galactosyated human serum albumin (gala-HSA) nanoparticles,which bind galactosyl and show good magnetic responsiveness,to carry chemotherapeutic drugs;and examine the properties of the gala-HSA nanoparticles by determing the number of galactose residues.
Method:Galactosyated human serum albumin was prepared by covalent coupling lactose to albumin using reductive amination method. The Fe_3O_4magnetic nanoparticles prepared by the titration hydrolyzation, gala-HAS,magnetite and purified adriamycin hydrochloride were mixed by appropriate proportion.Thereafter,the nanoparticles preparation process included sonication,albumin heat polymerization,washing with ether.The number of galactose residues was determined by phenol-sulfuric colorimetric method.The content of nanoparticles was by measured by liquid chromatography.The gala-HAS nanoparticles were resolved into normal saline.The motions of the particles were observed in saline using light microscopy,and the intrinsic detailed structure was observed by transmission electron microscopy.
Results:The average number of galactose residues was 32.the diameter the Fe_3O_4 magnetic nanoparticles ranged from 50nm to 100nm; And the average diameter of nanoparticles was 70 nm.The adriamycin content of galactosyated human serum albumin magnetic nanoparticles was 58.45ug/g;97.53%of the drug is trapped into nanoparticles;Under light microscopy,we could find that nanoparticles moved towards magnet rapidly in saline and gather together edge of to the side of magnet.If the magnet was moved away a certain distance,the speed of nanoparticles slowed down and aggregated and clusterd into longitudinally aligned short cylindrical chains.Under transmission electron microscopy,it was found the Fe_3O_4 was well-distribution in the galactosyated human serum albumin magnetic nanoparticles containing adriamycin.
Conclusion:galactosyated human serum albumin magnetic nanopartics containing Adriamycin have high the number of galactose resideues and excellent stable target effect,realease of chemotherapeutic drug from the nanopartics can be controlled.It provided a reliable carrying drug system for the targeting treatment of cancer.
方法:将乳糖和白蛋白用还原胺法合成半乳糖基人血白蛋白(galactosylated human serum albumin Gal-HSA);采用滴定水解法制备直径在70nm左右Fe_3O_4磁性纳米粒。将半乳糖白蛋白、Fe_3O_4磁性纳米粒及纯盐酸阿霉素按一定的比率混合,通过在精制棉子油中超声乳化、加热固化变性、乙醚洗涤等工艺制备出半乳糖白蛋白磁性阿霉素纳米粒;用苯酚—硫酸比色法测定半乳糖白蛋白的糖化比率;用乙醇提取法提取半乳糖白蛋白磁性阿霉素纳米粒中的阿霉素,并用液相色谱仪测定其含量。将纳米粒溶于生理盐水中,并在光学显微镜下观察在磁场的作用下,半乳糖基磁性纳米粒的运动情况,用激光粒度分析仪、原子力显微镜和透射电子显微镜观察纳米粒粒径的大小和内部结构。
结果:半乳糖白蛋白磁性阿霉素纳米粒的糖化比率为32;Fe_3O_4纳米粒径在70±30nm左右,粒径均匀;阿霉素的含量为58.45ug/g,阿霉素的包含率为97.53%;半乳糖白蛋白磁性阿霉素纳米粒溶液在光学显微镜下观察,在磁场的作用下,纳米粒迅速向磁铁的方向移动并发生聚集,当磁铁与纳米粒的距离加大时,纳米粒运动速度减慢,并沿磁力线的方向成串珠状聚集。透射电子显微镜下观察Fe_3O_4颗粒均匀分布在半乳糖白蛋白磁性阿霉素纳米粒中。
结论:半乳糖白蛋白磁性阿霉素磁性纳米粒具有较高糖化比率,稳定的磁性,靶向性强,药物包含率高,释药速率可控制的特点,为靶向药物治疗,提供了可靠的载药工具。
Objective:To prepare the galactosyated human serum albumin (gala-HSA) nanoparticles,which bind galactosyl and show good magnetic responsiveness,to carry chemotherapeutic drugs;and examine the properties of the gala-HSA nanoparticles by determing the number of galactose residues.
Method:Galactosyated human serum albumin was prepared by covalent coupling lactose to albumin using reductive amination method. The Fe_3O_4magnetic nanoparticles prepared by the titration hydrolyzation, gala-HAS,magnetite and purified adriamycin hydrochloride were mixed by appropriate proportion.Thereafter,the nanoparticles preparation process included sonication,albumin heat polymerization,washing with ether.The number of galactose residues was determined by phenol-sulfuric colorimetric method.The content of nanoparticles was by measured by liquid chromatography.The gala-HAS nanoparticles were resolved into normal saline.The motions of the particles were observed in saline using light microscopy,and the intrinsic detailed structure was observed by transmission electron microscopy.
Results:The average number of galactose residues was 32.the diameter the Fe_3O_4 magnetic nanoparticles ranged from 50nm to 100nm; And the average diameter of nanoparticles was 70 nm.The adriamycin content of galactosyated human serum albumin magnetic nanoparticles was 58.45ug/g;97.53%of the drug is trapped into nanoparticles;Under light microscopy,we could find that nanoparticles moved towards magnet rapidly in saline and gather together edge of to the side of magnet.If the magnet was moved away a certain distance,the speed of nanoparticles slowed down and aggregated and clusterd into longitudinally aligned short cylindrical chains.Under transmission electron microscopy,it was found the Fe_3O_4 was well-distribution in the galactosyated human serum albumin magnetic nanoparticles containing adriamycin.
Conclusion:galactosyated human serum albumin magnetic nanopartics containing Adriamycin have high the number of galactose resideues and excellent stable target effect,realease of chemotherapeutic drug from the nanopartics can be controlled.It provided a reliable carrying drug system for the targeting treatment of cancer.
引文
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