摘要
目的制备载microRNA—34 a脂质体(miLPs-34 a),研究其肺癌干细胞靶向性以及对肺癌干细胞的生长抑制能力。方法采用薄膜分散法制备载microRNA—34 a脂质体,考察脂质体的粒径,电位以及包封率;考察载microRNA-34 a脂质体的血清稳定性。通过细胞摄取实验考察肺癌干细胞对miLPs—34 a的摄取效率。MTT实验考察microRNA—34 a对肺癌干细胞的细胞毒性,构建肺癌干细胞肿瘤球模型,考察脂质体对肿瘤球的生长抑制能力。构建肺癌裸鼠异位模型,考察脂质体对肿瘤生长抑制效果。结果 miLPs—34 a的粒径在136.55±11.4 nm,电位为21.45±4.55mV,microPNA—34 a的包封率为94.6%。miLPs-34 a在24 h内,50%的血清中具有良好的血清稳定性。细胞摄取实验结果显示,A 549肺癌干细胞对miLPs-34 a的摄取效率是microRNA—34 a的3.1倍(P<0.01);MTT实验表明miLPs-34 a对肺癌干细胞的毒性显著强于mlcroRNA-34 a(P<0.01);肿瘤球抑制实验结果表明miLPs—34 a对肿瘤球的生长抑制能力显著强于microRNA-34 a,差异具有统计学意义(P<0.01),miLPs-34 a具有良好的抗肺癌作用。荷瘤裸鼠肿瘤生长抑制实验结果表明miLPs—34 a对裸鼠肿瘤生长的抑制能力显著强于microRNA—34 a,二者差异具有统计学意义(P<0.05)。结论载microRNA^34 a脂质体具有良好的肺癌干细胞靶向性和抗肺癌干细胞生长作用,是一种潜在高效的肺癌干细胞靶向给药系统。
Objective To preparemicroRNA-34 a loaded liposome and evaluate the targeting efficiency for lung cancer stem cells and effect on the treatment of lung cancer. Method The liposomes were prepared by thin film hydration method. The particle size,Zeta potential and entrapment efficiency were evaluated. Stability of liposome in serum was evaluated. The efficiency of cellular uptake on lung cancer stem cells in vitro was evaluated. The anti-proliferation efficiency of miLPs-34 a was evaluated by MTT assay. Tumor spheroids were used to evaluate anti-tumor ability of miLPs-34 a. Lung cancer stem cells were used to build orthotopictumor model, which were used to evaluate the effect of anti-cancer. Results The particle diameter of the miLPs-34 a was (136.55±11.4) nm with the Zeta potential of (21.45±4.55) mV. The entrapment efficiency of microRNA-34 awas 94.6%.the results demonstrated that the liposomes could keep stable in 50%serum for 24 h. miLPs-34 a uptaken by lung cancer stem cells were 3.1 times higher than that of microRNA-34 a(P<0.01). The MTT assay confirmed strong inhibitory effect of miLPs-34 a than microRNA-34 a(P<0.01). the inhibition of tumor spheroid confirmed strong inhibitory effect of miLPs-34 a than microRNA-34 a(P<0.01). The anti-tumor of miLPs-34 a was much more effectively than microRNA-34 a(P<0.01).Conclusion the microRNA-34 a loaded liposome could target to lung cancer stem cells and inhibit the proliferation of lung cancer stem cell. MiLPs-34 a, as a new nanometer drug, has a special application value for the therapy of lung cancer stem cell.
出处
《中国生化药物杂志》
CAS
北大核心
2014年第1期68-71,共4页
Chinese Journal of Biochemical Pharmaceutics
