中文摘要：

目的研究透明质酸键合分枝状聚乙烯亚胺的复合载体对癌细胞的靶向性,探究其是否受透明质酸相关受体的介导作用。方法通过对比观察复合载体在B16F1和HEK-293两种细胞内的传递及基因沉默现象,确定该载体在有无透明质酸受体情况下的运载状态。通过单体透明质酸与复合载体的竞争实验,进一步验证推断。根据复合载体在生物体内的分布及其对肿瘤增长的抑制效果,确定透明质酸受体对复合载体靶向性的影响。结果复合载体能够很好的运载si RNA进入含有透明质酸受体的B16F1细胞内,并且于该细胞内的基因沉默效率高达92%。随着培养基中单体透明质酸含量的增加,复合载体所实现的基因沉默效率逐渐降低。载体进入生物体内后,主要分布在细胞表面含有透明质酸受体的组织中。复合载体对于肿瘤的治疗效果好于单体分枝状聚乙烯亚胺作为载体的效果。结论复合载体对癌细胞的靶向性是由于透明质酸相关受体介导所实现的,其对于靶向治疗带有透明质酸受体的癌症,降低癌症治疗的副作用具有深远的意义。

英文摘要：

Objective To investigate the targeting of hyaluronic acid （HA）-graft-branch polyethylenimine （PEI） to cancer cells, and the effect of modification with HA on the receptor mediated endocytosis. Methods The efficiency of intracellular delivery and targeted gene silencing by siRNA/PEI-HA in the B16F1 cells with HA receptors and HEK-293 cells without HA receptors was compared to evaluate the effects of HA concentration in the transfection medium. The biodistribution and inhibition on tumor growth in vivo were evaluated to demonstrate the effects of HA receptor on the target of siRNA/PEI-HA complex. Results The siRNA/PEI-HA complex was well up taken into B16F1 cells, and the efficiency of gene silencing was about 92%. The gene silencing effect was reduced in the presence of free HA in the transfection medium. The complex was distributed mainly in the tissues with HA receptors. The tumor treatment effect of the complex was significantly better than that of branch polyethylenimine. Conclusions The targeting ability of PEI-HA could be enhanced by HA receptors mediated endocytosis, which has profound effects for the treatment of diseases in the tissues with HA receptors and the reduction of the adverse effects.