School of Biosciences and Biophamaceutics, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
School of Biosciences and Biophamaceutics, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Chem Phys Lipids. 2019 Nov;224:104685. doi: 10.1016/j.chemphyslip.2018.09.009. Epub 2018 Oct 9.
As an efficient gene delivery, non-viral vectors should have high transfection efficiency, excellent endosomal escape, low cytotoxicity, and the ability to rapidly release the gene into the cytoplasm.Cationic liposome have been widely used as efficient gene carriers, but the cytotoxicity, rapid degradation and low cellular uptake are major drawback impeding its further appolication. Herein, with double lauric acid as hydrophobic chains, tartaric acid as skeleton, 0 generation PAMAM modified with lysine as hydrophilic head, a new type cationic peptide lipid was synthetised. The alkyl chain promote lipid across cell membranes and with membrane fusion, 0 generation PAMAM modified with lysine hydrophilic end amino can contain a large number of protons which can change into ammonium and combine with the DNA negatively charge phosphate groups. It is expected that this carrier has low toxicity, high transfection efficiency and targeting property. By adjusting the cationic liposome/gene weight ratio, the transfection system was optimized to improved gene transfection efficiency, reduce cytotoxicity, and increase property and stability, etc.
作为一种有效的基因传递方法，非病毒载体应该具有高转染效率、出色的内体逃逸能力、低细胞毒性以及将基因快速释放到细胞质中的能力。阳离子脂质体已被广泛用作有效的基因载体，但细胞毒性、快速降解和低细胞摄取是阻碍其进一步应用的主要缺点。在这里，我们以双月桂酸作为疏水链，酒石酸作为骨架，用赖氨酸修饰的 0 代 PAMAM 作为亲水头部，合成了一种新型阳离子肽脂质。烷基链促进脂质穿过细胞膜并与细胞膜融合，用赖氨酸修饰的 0 代 PAMAM 的亲水头端氨基可以包含大量质子，这些质子可以转化为铵并与 DNA 的负电荷磷酸基团结合。预计该载体具有低毒性、高转染效率和靶向性。通过调整阳离子脂质体/基因的重量比，优化了转染体系，以提高基因转染效率、降低细胞毒性、增加性能和稳定性等。
