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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
  • 期刊名称:高等学校化学学报
  • 时间:0
  • 页码:527-552
  • 语言:中文
  • 分类:Q782[生物学—分子生物学] O631.3[理学—高分子化学;理学—化学]
  • 作者机构:[1]南开大学生命科学学院,生物活性材料教育部重点实验室,天津300071
  • 相关基金:国家自然科学基金(批准号:30370405,20774050)资助.
  • 相关项目:自组装型树枝状高分子基因传递系统的性能研究
中文摘要:

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.

英文摘要:

A new type of tumor-targeted non-viral gene vector, PSL-PEI600-Chol, was synthesized by ringopening of poly [ succinimide-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-Cl 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.

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