Disulfide Cross-linked Low Generation Dendrimers With Low Cost,Cytotoxicity, and High Gene Delivery Efficiency
Cationic poly(amidoamine) (PAMAM) dendrimers were widely used as non-viral gene carriers ”1”.PAMAM dendrimer-based product Superfect(R) was already commercially available gene transfection reagent.However,these products are based on high generation dendrimers with high cost and serious cytotoxicity ”2,3”.In this study,we prepared high efficient gene carriers using disulfide cross-linked generation 2 (G2) PAMAM dendrimers.These disulfide cross-linked G2 dendrimer may degrade into G2 dendrimer after their localization in the endosome of the cancer cells.They can effectively condense DNA into ~200 nm polyplexes.Compared to G5 PAMAM dendrimer,disulfide cross-linked G2 PAMAM dendrimer showed much improved gene transfection efficiency (both GFP gene and luciferase) and reduced cytotoxicity in both 293T and HeLa cell lines (Figure 1).The disulfide cross-linked G2 dendrimer prepared at a linker/dendrimer 1(∶)1 molar ratio showed the highest gene delivery efficiency and exhibited comparable transfection efficiency to branched 25 kD PEI,a commercially available non-viral gene vector.Confocal laser scanning microscope (CLSM) studies further revealed the high cellular uptake behavior of disulfide cross-linked G2 PAMAM dendrimers and partial dendrimers were observed in cell nucleus,suggesting the degradation of disulfide cross-linked dendrimers into G2 dendrimers with small size and low cytotoxicity.Our study have demonstrated that disulfide cross-linked low generation dendrimers with low cost,cytotoxicity,and high transfection efficiency are efficient alternatives to high generation dendrimers in gene delivery.We can further improve the delivery efficiency of these promising materials by surface modification of low generation dendrimers with targeting moieties,amino acids,sugars and followed by disulfide cross-linking ”4”.
dendrimer PAMAM genedelivery disulfide cross-linked
LIU Hongmei WANG Hui YANG Wenjun CHENG Yiyun
Shanghai Key Laboratory of Regulatory Biology, School of Life Science, East China Normal University, Shanghai, 200241, ER.China
国内会议
武汉
英文
533-534
2012-10-16（万方平台首次上网日期，不代表论文的发表时间）