HA-His/PEI-His/DNA纳米复合载体的制备及基因转染研究

Preparation of HA-His/PEI-His/DNA Nano-Complexes for Gene Transfection

为了克服PEI介导的基因转染毒性高、无肿瘤细胞选择性的缺点,采用组氨酸(His)分别对聚乙烯亚胺(PEI)和透明质酸(HA)进行修饰,得到PEI-His(PH)和HA-His(HH)。利用静电相互作用制得HH、PH与DNA的复合物HH/PH/DNA(HPD)并用于基因转染。动态光散射测定HPD复合物的平均粒径为109 nm,ζ-电位为-15 mV。HPD复合物可有效包载DNA并保护其不被酶降解,表面的HA还可避免血清粘附。细胞实验结果表明,经His修饰可有效降低PEI的细胞毒性,HPD复合物介导的基因转染对肿瘤细胞具有选择性,在肿瘤细胞中的转染效率为正常细胞中的2倍。

To decrease the toxicity and improve the tumor cell selectivity of PEI,polyethyleneimine(PEI) and hyaluronic acid(HA) were modified with histidine(His) to obtain PEI-His and HA-His in this study. The HH/PH/DNA(HPD) complexes,used for gene transfection,were prepared via electrostatic interaction. The average particle size of the complexes was 108.5 nm determined by dynamic light scattering,as well as the ζ-potential was-15.4 m V. HPD could efficiently encapsulate DNA and protect it from the enzymatic degradation. In addition,the HH coating further prevented the adhesion of serum on the surface of HPD. Cellular experiments showed that the cytotoxicity of PEI was reduced via the modification of His. The gene transfection efficiency induced by HPD in tumor cells increased by 2-fold as compared with that in normal cells,showing good selectivity.