Gene therapy has tremendous potential for both inherited and acquired diseases, however, delivery problems limited their clinical application. The clinical success of gene therapy requires a safe and effective gene delivery system. Cationic lipids have particularly excellent potential for gene delivery applications because of their lesser immunogenic nature, robust manufacture ability to deliver large pieces of DNA, and ease of handling and preparation techniques. Existing cationic lipids were still far from the requirement of in vivo gene therapy because of their relatively low transfection efficiency, lack of cell-targeting property and potential cytotoxicity. Consequently, the development of novel cationic lipid structures is of great importance for further development of gene therapy. In this study, in order to develop superior cationic lipids for gene delivery, two bis-cyclen-based cationic lipids were designed and synthesized, and their structures were characterized by H NMR and HRMS. Liposomes were easily prepared by mixing cationic lipids with neutral lipid dioleoylphos-phoethanolamine ( DOPE ). Agarose gel electrophoresis demonstrated that the formed liposomes could completely condense and protect DNA at N/P ratio of 6. The results suggested that the synthesized cationic lipids might be of potential as non-viral gene carrier.%设计合成了一类新型的阳离子脂质小分子化合物1.化合物1含有双cyclen亲水端和甾体疏水基团.凝胶电泳实验显示,含胆固醇和皂素的双大环多胺阳离子脂质化合物1与二油酰磷脂酰乙醇胺( DOPE)形成的阳离子脂质体能够与DNA有效作用,在氮磷比为6时即可完全包裹DNA,具有作为非病毒基因载体的潜在应用价值,为设计新型阳离子脂质基因载体提供了新思路.
展开▼
