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Linear TACN-based cationic polymers as non-viral gene vectors

机译:基于线性TACN的阳离子聚合物作为非病毒基因载体

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A series of linear cationic polymers were synthesized by the ring-opening polymerization between diglycidyl ethers and 1-Cbz-1,4,7-triazacyclononane (TACN). Besides the good pH buffering capacity in endosome pH range caused by TACN, these polymers have evenly distributed hydroxyl groups, which may benefit not only the water solubility but also their biocompatibility and serum tolerance. The polymers could condense DNA into nanoparticles with appropriate sizes and zeta-potentials. Cytotoxicity assays reveal that most of the polyplexes formed from title polymers have lower cytotoxicity than those derived from PEI. In vitro transfection assays show that some of these materials have higher transfection efficiency than bPEI, especially in tumor cells with the presence of serum. Flow cytometry and confocal microscopy were applied to further confirm their good serum tolerance. The structureactivity relationship of such type of polymeric vectors was also discussed. Results suggest that the ringopening polymerization may be an effective synthetic approach toward gene delivery materials with high biological activity.
机译:通过二缩水甘油醚与1-Cbz-1,4,7-三氮杂环壬烷(TACN)之间的开环聚合反应,合成了一系列线性阳离子聚合物。这些聚合物除了在TACN引起的内体pH范围内具有良好的pH缓冲能力外,还具有分布均匀的羟基,这不仅有利于水溶性,而且还具有生物相容性和血清耐受性。聚合物可以将DNA浓缩成具有适当大小和zeta电位的纳米颗粒。细胞毒性试验表明,大多数由标题聚合物形成的多链体的细胞毒性要低于衍生自PEI的那些。体外转染试验表明,其中某些材料的转染效率高于bPEI,尤其是在存在血清的肿瘤细胞中。应用流式细胞术和共聚焦显微镜进一步证实其良好的血清耐受性。还讨论了这类聚合物载体的结构活性关系。结果表明,开环聚合反应可能是一种具有高生物活性的基因合成材料的有效合成方法。

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