乳糖化-去甲斑蝥素磷脂复合物pH敏感型脂质体肝靶向抗肿瘤活性研究  

Liver targeting anti-tumor activity of pH-sensitive liposomes loaded with lactosyl-norcantharitin phospholipids complex

作　　者：周奕[1] 叶建林[1] 

机构地区：[1]南京医科大学附属无锡市人民医院儿童医院,江苏无锡214023

出　　处：《中草药》2014年第19期2803-2808,共6页Chinese Traditional and Herbal Drugs

基　　金：国家科技部"十一五"重大新药创制技术平台项目资助(2009ZX09310-001);国家科技部科技型中小企业技术创新基金(07C26223201333);江苏省"六大人才高峰"资助项目

摘　　要：目的考察乳糖化-去甲斑蝥素磷脂复合物pH敏感型脂质体(pH-LPC-lips)的体内外抑瘤作用,及其在小鼠体内的肝脏靶向性。方法以空白脂质体(blank-lips、blank-pH-lips)为对照,MTT法考察乳糖化-去甲斑蝥素(Lac-NCTD)和2种载药脂质体(Lac-lips、pH-LPC-lips)对人体肝癌细胞HepG2的细胞毒作用。采用HPLC法评价HepG2细胞对Lac-NCTD及其脂质体的摄取过程。建立H22肝癌细胞小鼠荷瘤模型考察脂质体在体内抗肿瘤活性。用Cy-7标记羧甲基壳聚糖(CMCT)制备Cy-7荧光标记的pH-LPC-lips,通过小动物活体成像仪,采集荧光信号,考察该脂质体在小鼠体内的靶向性。结果与Lac-NCTD、Lac-lips相比,pH-LPC-lips在体外对肿瘤细胞HepG2的亲和性更好,细胞毒作用更显著。体内抑瘤实验表明,pH-LPC-lips可以更好地抑制H22肿瘤的生长。pH-LPC-lips可以靶向聚积在小鼠肝脏和肿瘤部位,有很好的靶向作用,从而减小药物毒副作用,提高抗肿瘤效果。结论优化的pH-LPC-lips可以在呈弱酸性的肿瘤部位主动释药,并对肝脏和肿瘤部位具有靶向性,从而表现出更好的抗肿瘤作用。Objective To investigate the antitumor activity of pH-sensitive liposomes （pH-LPC-lips） loaded with lactosyl-norcantharitin （Lac-NCTD） phospholipids complex in vitro and in vivo, and the liver targeting in mice. Methods Using blank liposomes （blank-lips and blank-pH-lips） as control, the MTT assay was used to study the cytotoxic effects of Lac-NCTD and its liposomes （Lac-lips and pH-LPC-lips） on human hepatoma carcinoma cells HepG2. HPLC assay was used to evaluate the uptake of Lac-NCTD and its liposomes in HepG2. In vivo antitumor activity of Lac-NCTD and its liposomes were evaluated in mice bearing H22 liver tumors. The hepatocyte specificity of near-infrared fluorescence dye （Cy7）-labeled pH-LPC-lips in H22 tumor-bearing mice was monitored through NIR fluorescence real-time tumor imaging instrument. Results The pH-LPC-lips demonstrated stronger cytotoxicity against tumor cells HepG2 and easily permeated the cell membrane, compared with Lac-NCTD and Lac-lips. The results of antitumor activity in vivo showed that pH-LPC-lips displayed best tumor inhibitory effect. The optical imaging results indicated that Cy7-1abeled pH-LPC-lips showed excellent hepatocyte specificity in H22 tumor-bearing mice, which could reduced the side effect, and increased the antitumor activity. Conclusion The pH-LPC-lips could take the initiative to release at the tumor site and showed the liver-targeting. As a result, the preparation could be regarded as novel liver-targeting agent which has better antitumor effect.

关 键 词：乳糖化-去甲斑蝥素 pH敏感型脂质体 磷脂复合物 抗肿瘤活性 肝靶向性 

分 类 号：R285.5[医药卫生—中药学]