Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, PR China.
Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, PR China.
Eur J Med Chem. 2014 Nov 24;87:413-20. doi: 10.1016/j.ejmech.2014.09.091. Epub 2014 Sep 30.
A series of cationic polymers based on low generation (G1) peptide dendrimer were synthesized with disulfide-containing linkages. The DNA binding abilities of the target polymers were studied by gel electrophoresis and fluorescence quenching assay. The bioreducible property of the disulfide-containing polymers P2 and P3 was also investigated in the presence of dithiothreitol (DTT). Results from dynamic light scattering (DLS) and transmission electron microscopy (TEM) assays reveal that these materials may condense DNA into nanoparticles with proper sizes and zeta-potentials. In vitro cell experiments show that compared to branched 25 KDa PEI, P2 and P3 may exhibit much higher gene transfection efficiency and lower cytotoxicity in both HEK293 and U-2OS cells. Additionally, polymer prepared from Michael addition gives better gene transfection ability, while polymer prepared from ring-opening reaction has better serum tolerance. Results indicate that these polymers might be promising non-viral gene vectors for their easy preparation, very low cytotoxicity, and good transfection efficiency.
一系列基于低代（G1）肽树状大分子的阳离子聚合物，通过含有二硫键的连接键合成。通过凝胶电泳和荧光猝灭实验研究了目标聚合物的 DNA 结合能力。在存在二硫苏糖醇（DTT）的情况下，还研究了含有二硫键的聚合物 P2 和 P3 的生物还原性。动态光散射（DLS）和透射电子显微镜（TEM）实验结果表明，这些材料可以将 DNA 凝聚成具有适当大小和 ζ 电位的纳米颗粒。体外细胞实验表明，与支化 25 kDa 的聚乙烯亚胺相比，P2 和 P3 在 HEK293 和 U-2OS 细胞中可能表现出更高的基因转染效率和更低的细胞毒性。此外，通过迈克尔加成制备的聚合物具有更好的基因转染能力，而通过开环反应制备的聚合物具有更好的血清耐受性。结果表明，这些聚合物可能是很有前途的非病毒基因载体，因为它们具有易于制备、极低的细胞毒性和良好的转染效率。
