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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。
Objective To study the targeting of hyaluronic acid-conjugated branched polyethyleneimine (PEI) to cancer cells and explore whether it is mediated by hyaluronan-related receptors. Methods By comparing the transmission and gene silencing of the complex vector in B16F1 and HEK-293 cells and determining the carrier status of the vector in the presence or absence of hyaluronic acid receptor. Through the monomer hyaluronic acid and composite carrier competition experiments, further validation inference. According to the distribution of the composite carrier in vivo and its inhibitory effect on tumor growth, the effect of hyaluronic acid receptor on the targeting of the composite carrier was determined. Results The composite vector could well carry si RNA into B16F1 cells containing hyaluronan receptor, and the efficiency of gene silencing in this cell was as high as 92%. With the increase of hyaluronic acid content in the medium, the efficiency of gene silencing achieved by the composite vector is gradually reduced. After the carrier into the body, the main distribution in the cell surface contains hyaluronic acid receptor in the tissue. The therapeutic effect of the composite carrier on tumors is better than that of monomeric branched polyethyleneimine as a carrier. Conclusion The targeting of the complex vector to cancer cells is mediated by hyaluronan-related receptors, which has far-reaching significance for the targeted therapy of cancer with hyaluronan receptor and the reduction of the side effects of cancer therapy.