Natural antioxidants and vitamins have potential to protect biological systems from peroxidative damage induced by peroxyl radicals, α-tocopherol (Vitamin E, lipid soluble) and ascorbic acid (vitamin C, water soluble), well known natural antioxidant molecules. In the present study we described the synthesis and biological evaluation of hybrid of these two natural antioxidants with each other via ammonium di-ethylether linker, Toc-As in gene delivery. Two control cationic lipids N14-As and Toc-NOH are designed in such a way that one is with ascorbic acid moiety and no tocopherol moiety; another is with tocopherol moiety and no ascorbic acid moiety respectively. All the three cationic lipids can form self-assembled aggregates. The antioxidant efficiencies of the three lipids were compared with free ascorbic acid. The cationic lipids (Toc-As, N14-As and Toc-NOH) were formulated individually with a well-known fusogenic co-lipid DOPE and characterization studies such as DNA binding, heparin displacement, size, charge, circular dichroism were performed. The biological characterization studies such as cell viability assay and in vitro transfection studies were carried out with the above formulations in HepG2, Neuro-2a, CHO andHEK-293T cell lines. The three formulations showed their transfection efficiencies with highest in Toc-As, moderate inN14-As and least in Toc-NOH. Interestingly, the transfection efficiency observed with the antioxidant based conjugated lipid Toc-As is found to be approximately two and half fold higher than the commercially available lipofectamine 2000 at 4:1 charge ratio in Hep G2 cell lines. In the other cell lines studied the efficiency of Toc-As is found to be either higher or similarly active compared to lipofectamine 2000. The physicochemical characterization results show that Toc-As lipid is showing maximum antioxidant potency, strong binding with pDNA, least size and optimal zeta potential. It is also found to be least toxic in all the cell lines studied especially in Neuro-2a cell lines when compared to other two lipids. In summary, the designed antioxidant lipid can be exploited as a delivering system for treating ROS related diseases such as malignancy, brain stroke, etc.

天然抗氧化剂和维生素具有保护生物系统免受过氧化物自由基，α-生育酚（维生素E，脂溶性）和抗坏血酸（维生素C，水溶性）引起的过氧化损害的作用，众所周知，天然抗氧化剂分子。在本研究中，我们描述了这两种天然抗氧化剂通过二乙醚铵连接体Toc-As在基因传递中相互杂交的合成和生物学评估。两种对照阳离子脂质N14-As和Toc-NOH以一种具有抗坏血酸部分而没有生育酚部分的方式设计；另一个是分别带有生育酚部分和没有抗坏血酸部分。这三种阳离子脂质均可形成自组装聚集体。将这三种脂质的抗氧化效率与游离抗坏血酸进行了比较。阳离子脂质（Toc-As，N14-As和Toc-NOH）分别用众所周知的融合脂质DOPE配制，并进行了诸如DNA结合，肝素置换，大小，电荷，圆二色性等表征研究。生物学特性研究，例如细胞活力测定和体外用上述制剂在HepG2，Neuro-2a，CHO和HEK-293T细胞系中进行转染研究。这三种制剂显示出它们的转染效率，在Toc-As中最高，在N14-As中适中，而在Toc-NOH中最低。有趣的是，发现在Hep G2细胞系中以4：1的电荷比，基于抗氧化剂的共轭脂质Toc-As所观察到的转染效率比市售lipofectamine 2000高出大约两倍和一半。在其他研究的细胞系中，与lipofectamine 2000相比，发现Toc-As的效率更高或具有相似的活性。理化特性结果表明Toc-As脂质显示出最大的抗氧化剂效能，与pDNA的强结合力，最小的大小和最佳的Zeta电位。与其他两种脂质相比，在所有研究的细胞系中，尤其是在Neuro-2a细胞系中，它的毒性也最低。总之，可以将设计的抗氧化剂脂质用作治疗ROS相关疾病（如恶性肿瘤，脑中风等）的递送系统。