靶向及pH敏感仿脂蛋白结构纳米载体运载紫杉醇的体内抗肿瘤研究

In vivo anti-tumor activity of tumor-targeting pH-sensitive lipoprotein-mimic nanocarrier with paclitaxel loaded

紫杉醇作为广谱抗癌药物具有良好的抗肿瘤活性,但存在的许多问题限制了其临床应用。该研究利用制备的具有靶向及p H敏感功能的新型仿脂蛋白结构纳米载体(FA-BSA-LC/DOPE),包载紫杉醇(paclitaxel,PTX)进行体内抗肿瘤效果研究。通过小动物活体成像技术,考察载近红外荧光染料的新型脂蛋白结构纳米载体在荷瘤裸鼠体内不同时间的肿瘤靶向效果及在各组织的不同分布情况;对各组不同载药制剂进行荷瘤裸鼠的体内抗肿瘤研究并对各组治疗后的肿瘤组织进行病理染色分析,考察其体内抗肿瘤效果。结果表明,新型仿脂蛋白结构纳米载体在肿瘤组织具有明显靶向能力且具有相对长的保留时间;在体内抗肿瘤活性研究中,FA-BSA-LC/DOPE-PTX组表现出显著的荷瘤裸鼠的肿瘤抑制作用,肿瘤生长抑制率为79. 3%,并且通过各组肿瘤组织切片经HE染色后的组织学形态观察发现,FA-BSA-LC/DOPE-PTX组具有严重的细胞坏死区域。因此,FA-BSA-LC/DOPE作为具有生物相容性,肿瘤靶向以及p H敏感释药功能的一种新型脂蛋白结构纳米载体运载紫杉醇,在体内具有显著的抗肿瘤效果。

Paclitaxel( PTX) is used as a broad spectrum anti-tumor medicine. However,serious drawbacks restrict clinical application of PTX. In this study,we prepared tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel( BSALC/DOPE-PTX) to study the effective antitumor activity. The in vivo targeting ability of the nanocarrier in tumor bearing nude mice was evaluated by using a Kodak in vivo imaging system FX PRO. The in vivo anti-tumor activity was evaluated in MDA-MB-231 tumor bearing mice,and representative sections were stained with hematoxylin and eosin( H&E),and examined by light microscopy. The results showed that DiR-loaded FA-BSA-LC/DOPE selectively targeted tumor,and had a relatively long residence in the tumor tissue. According to the in vivo anti-tumor activity study,FA-BSA-LC/DOPE-PTX exhibited an outstanding tumor inhibition effect with a tumor growth inhibition rate of 79.3%,and tumor tissue sections stained by hematoxylin and eosin( HE) showed severe necrosis areas and many dead cells with condensed nuclei in the FA-BSA-LC/DOPE-PTX group. Therefore,FA-BSA-LC/DOPE-PTX is a biocompatible,tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier,with a very marked anti-tumor activity in tumor-bearing mice in vivo.