胆固醇修饰的低分子量聚乙烯亚胺接枝化聚[L-天冬酰胺-co-L-赖氨酸]作为基因载体的性能研究

通过将低分子量的聚乙烯亚胺(PEI600)及其胆固醇衍生物与聚(L-天冬酰胺-co-L-赖氨酸)(PSL)进行开环反应, 合成了一类新型的肿瘤靶向基因载体, 研究了这类载体与DNA形成复合物的性质以及介导绿色荧光蛋白质粒pEGFP-C1转染不同细胞的性能. 结果表明, 在复合质量比大于5∶1时, 各载体均能与DNA形成结构稳定的复合物. 同时转染实验结果证明, 通过在侧链引入一定数目的胆固醇, 可以明显提高载体对于癌细胞HepG2和Hela的转染效率. 这类新型的载体具有良好的细胞相容性、较高的转染效率以及易于进行靶向修饰等特点, 在基因治疗研究领域中将具有较好的潜在应用价值.

Properties of Poly[L-(aspartic acid)-co-L-lysine] Grafted with Cholesterol Conjugated Low Molecular Weight Poly(ethylenimine) for Gene Delivery

A new type of tumor-targeted non-viral gene vector,PSL-PEI600-Chol,was synthesized by ring-opening of polysuccinimide-co-lysine](PSL) with low-molecular weight poly(ethylenimine)(PEI600) and its cholesterol derivatives,respectively.The important parameters for preparation of PSL-PEI600-Chol/DNA complexes and characterization of physico-chemical properties of this delivery system were also investigated.It is indicated that PSL-PEI600-Chol could form compact complexes with DNA at a mass ratio higher than 5.The transfection efficiencies of PSL-PEI600-Chol were evaluated in different cell lines and the results showed that cholesterol modification could enhance the delivery of pEGFP-C1 into tumor cells HepG2 and Hela.These results suggest that with a lower cytotoxicity,higher gene delivery capacity and versatility for chemical conjugation,PSL-PEI600-Chol could warrant further investigation for a promising nonviral gene vector.