中文摘要：

背景与目的 去唾液酸糖蛋白受体（asialoglycoprotein receptor,ASGPR）是一种肝细胞特异性表达的膜表面蛋白,能够特异性地识别带有半乳糖残基的糖蛋白.乳糖酸含有半乳糖基团,可以作为靶向肝癌的特异性配基.该研究旨在探讨乳糖酸修饰的聚乙二醇/聚丙交酯-乙交酯/聚赖氨酸[methoxypoly（ethylene glycol）-b-poly（D,L-lactide-co-glycolide）-b-poly（L-lysine）（mPEG-PLGA-PLL）纳米粒,mPEG-PLGA-PLL-GAL NPs）]对肝癌Huh7靶向效果,为构建新型的靶向肝癌的纳米递送系统提供实验数据.方法 MTT法确定Huh7细胞摄取mPEG-PLGA-PLL NPs与mPEG-PLGA-PLL-GAL NPs适当的浓度;通过激光共聚焦和荧光显微镜定性观察Huh7对罗丹明B标记的mPEG-PLGA-PLL NPs和mPEG-PLGA-PLL-GAL NPs的摄取;并采用流式细胞计数仪定量研究Huh7细胞对两者的摄取差别;尾静脉注射荷Huh7瘤裸鼠研究两者体内分布情况.结果 mPEG-PLGA-PLL NPs与mPEG-PLGA-PLL-GAL NPs的浓度在0.2 mg/mL时细胞存活率较高且对Huh7细胞的毒性较小.激光共聚焦断层扫描显示Huh7细胞可以较好地摄取mPEG-PLGA-PLL-GAL NPs,同时流式细胞仪定量显示mPEGPLGA-PLL-GAL NPs在Huh7细胞的分布较mPEG-PLGA-PLL NPs高40%（P〈0.05）.mPEG-PLGA-PLL NPs与mPEG-PLGAPLL-GAL NPs在移植瘤中的分布明显多于其他脏器,并且随时间的延长mPEG-PLGA-PLL-GAL NPs体现了更好的靶向效果.结论 体外与体内实验证明乳糖酸修饰的mPEG-PLGA-PLL NPs对肝癌细胞Huh7有很好的靶向效果,可为肝癌的靶向治疗提供较好的药物载体.

英文摘要：

Background and purpose： It is a wonderful approach to deliver drugs to hepatocellular carcinoma cell by receptor-mediated targeting. The asialoglycoprotein receptor （ASGPR） specifically recognized by galactose moiety residue is a mainly expressing membrane protein on the surface of bepatocellular carcinoma cell. Methoxy-poly （ethylene glycol）-b-poly（D, L-lactide-co-glycolide）-b-poly（L-lysine） （mPEG-PLGA-PLL） （PEAL） coupled with lactobionic acid （LA） bearing galactose group （PEAL-GAL） nanoparticles （NPs） are used as a novel drug carrier to hepatocellular carcinoma cell Huh7. This paper examined its effect on targeting Huh7 cells. Methods： Cytotoxicities of PEAL and PEAL-GAL NPs were assayed based on viability of Huh7 cells measured by MTT method. The distribution of PEAL or PEAL-GAL NPs labeled by Rhodmaine B （RB） in Huh7 cells was observed with confocal laser scanning microscope （CLSM） or fluorescence microscope. Quantitative comparisons were made between cellular uptake of RB-loaded PEAL or PEAL-GAL NPs by flow cytometer （FCM）. Finally, nude mice bearing hepatocellular carcinoma were adopted to investigate the distribution of PEAL NPs or PEAL-GAL NPs in different organs and cancer. Results： PEAL NPs and PEAL-GAL NPs did not show much cytotoxicity at the concentration of 0-0.2 mg/mL. PEAL-GAL NPs were well uptaken after being incubated with Huh7 cells for 3 h. Besides, Z-section and measurement with CLSM clearly showed that PEAL-GAL NPs were well-distributed. After the same co-incubation time, Huh7 cells uptook much more PEAL-GAL NPs than PEAL NPs （P〈0.05）. At 4-48 h after PEAL NPs and PEAL-GAL NPs were respectively injected via tail vein of nude mice, PEAL NPs and PEAL-GAL NPs were mainly distributed in cancers and livers compared to other organs. However, PEAL-GAL NPs demonstrated better cancer targeting than that of PEAL NPs. Conclusion： Compared with PEAL, LA grafted PEAL showed better targeting ability to Huh7 cells. LA promotes Huh7 cells＇ upta