表皮生长因子受体靶向纳米载体荷载c-erbB2反义寡脱氧核苷酸对人乳腺癌SK-BR3细胞的摄取与滞留*

背景：结合肿瘤的分子靶向技术和纳米技术，制备出一种新的具有靶向作用的纳米载体，以达到对肿瘤更好靶向作用的目的。 目的：制备表皮生长因子偶联牛血清白蛋白纳米载体，联合核素标记的c-erbB2 反义寡脱氧核苷酸，体外观察人乳腺癌SK-BR3细胞对其摄取情况。 设计、时间及地点：对比观察实验，于2006-09/2008-03在重庆医科大学生物化学和分子生物学教研室，重庆医科大学分子医学与肿瘤研究中心，重庆医科大学放射医学教研室完成。 材料：牛血清白蛋白(生物技术级)由美国Amresco公司提供，表皮生长因子由英国PeproTech EC LTD提供，125I由成都中核高通同位素股份有限公司提供，寡脱氧核苷酸由上海生工生物工程技术服务有限公司提供。 方法：采用超声乳化-化学交联及羧和反应制备表皮生长因子偶联白蛋白靶向纳米载体，通过核素标记示踪技术检测表皮生长因子偶联白蛋白靶向纳米载体的相关性质。 主要观察指标：测量表皮生长因子靶向纳米载体荷载c-erbB2反义寡脱氧核苷酸的载药量、包封率及释药率，人乳腺癌SK-BR3细胞对表皮生长因子靶向纳米载体的摄取率及滞留率。 结果：表皮生长因子靶向纳米载体包载125I标记的反义寡脱氧核苷酸组的摄取率及滞留率高于正义寡脱氧核苷酸组和无义寡脱氧核苷酸组。同时c-erbB2寡脱氧核苷酸使用纳米载体荷载组的摄取率及滞留率均高于未使用纳米载体组，差异有显著性意义(P < 0.05)。 结论：125I标记的表皮生长因子靶向纳米载体能够提高乳腺癌SK-BR3细胞对c-erbB2反义寡脱氧核苷酸的摄取和滞留，能达到更好的靶向作用。

Intake and retention of human breast cancer SK-BR3 cells to epidermal growth factor receptor targeting nanoparticles loading c-erbB2 antisense oligodeoxyribonucleotide

BACKGROUND: A new target nanoparticle vector needs to be established based on molecular target and nanometer technology in order to achieve a great target effect on tumor. OBJECTIVE: To investigate the intake of human breast cancer SK-BR3 cells to c-erbB2 antisense oligodeoxyribonucleotide (ASODN) which was mediated by epidermal growth factor (EGF) coupling of bovine serum albumin (BSA) nanoparticles. DESIGN, TIME AND SETTING: A contrast study was performed at Research Room of Biochemistry and Molecular Biology, Research Center of Molecular Medicine and Oncology, and Research Room of Radiomedicine, Chongqing Medical University from September 2006 to March 2008. MATERIALS: BSA (biotechnological grade) was provided by Amresco, USA; EGF by PeproTech EC LTD, UK; 125I by Zhonghe Gaotong Isotope Co., Ltd., Chengdu; oligodeoxyribonucleotide by Shenggong Bioengineering Co., Ltd., Shanghai. METHODS: Ultrasound emulsification-chemical cross-linking and carboxymethyl reaction were used to prepare EGF-conjugated albumin targeting nanoparticles. In addition, isotopic labeling tracer technique was used to detect the relative performance of the nanoparticle vector. MAIN OUTCOME MEASURES: The drug loading rate, encapsulation efficiency and the release rate were detected, and uptake and stranded rates of human breast cancer SK-BR3 cells were measured. RESULTS: The intake and retention rates in the EGF targeting nano-carrier packeting 125I-ASODN group were higher than those in the 125I-sense oligodeoxynucleotide (SODN) group and the 125I-nonsense oligodeoxynucleotide (NSODN) group. At the same time, the uptake of retention rates in the c-erbB2 oligodeoxynucleotide with nano-carrier group were significantly higher than those in the non-nano-carrier group (P < 0.05). CONCLUSION: 125I-EGF-BSA targeting nano-carrier can increase the uptake and retention rates of c-erbB2 anti-oligodeoxynucleotides in breast cancer SK-BR3 cells, and achieve better targeting effects.