叶酸修饰的长春新碱纳米脂质体的制备及其对人肝、肺癌细胞的作用

Preparation of Folic Acid-loaded Vincristine Nano Liposome and Its Effects on Human Liver and Lung Cancer Cells

目的：制备叶酸（FA）修饰的长春新碱（VCR）纳米脂质体（VCR-n Lip-FA）并考察其对人肝、肺癌细胞的作用。方法：采用硫酸铵梯度法制备VCR-n Lip-FA,考察其粒径分布、Zeta电位、包封率、释放率。以人肝癌Hep G2细胞、人肺癌A549细胞为例,比较VCR-n Lip-FA和VCR-n Lip的细胞摄取率和体外抑制效果（5～80μg/ml）。结果：VCR-n Lip-FA的粒径分布为98.1～159.0 nm,平均粒径为132.2 nm,平均Zeta电位为-40.1 m V,平均包封率为（86.6±3.5）%（n=4）,24 h的累积释放率为（42.2±2.6）%。与VCR-n Lip比较,A549细胞对VCR-n Lip-FA的摄取率和VCR-n Lip-FA对A549细胞活力的抑制作用差异无统计学意义（P〉0.05）;Hep G2细胞对VCR-n Lip-FA的摄取率和VCR-n Lip-FA对Hep G2细胞活力的抑制作用明显增加（P〈0.01）,且抑制作用呈浓度依赖性。结论：所制备的VCR-n Lip-FA可高效地将抗癌药物靶向到Hep G2细胞,并高效地抑制其生长;但对A549细胞的作用无明显提高。

OBJECTIVE：To prepare folic acid（FA）-loaded vincristine（VCR）nano liposome（VCR-n Lip-FA）and to study its effects on human liver and lung cancer cells.METHODS：VCR-n Lip-FA was prepared by ammonium sulfate gradient method,and particle size,Zeta-potential,encapsulation rate and release rate were investigated.Taking human liver cancer Hep G2 cells and lung cancer A549 cells as example,uptake rate and inhibitory effect in vitro（5-80 μg/ml）were compared between VCR-n Lip-FA and VCR-n Lip.RESULTS：The particle size distribution,average particle size,average Zeta-potential,average encapsulation rate and24 h accumulative release rate of VCR-n Lip-FA were 98.1-159.0 nm,132.2 nm,-40.1 m V,（86.6±3.5）%（n=4）and（42.2±2.6）%.Compared with VCR-n Lip,there was no statistical significance in uptake rate of A549 cells to VCR-n Lip-FA and inhibitory effect of VCR-n Lip-FA on A549 cell viability（P〈0.05）;uptake rate of Hep G2 cells to VCR-n Lip-FA and inhibitory effect of VCR-n Lip-FA on Hep G2 cell viability increased significantly（P〈0.01）,in dose-dependent manner.CONCLUSIONS：Prepared VCR-n Lip-FA can target anti-tumor drug to Hep G2 cells efficiently,and highly inhibit the growth of Hep G2 cells.But it has no higher effects on A549 cells.