1. α-Tocopherol-ascorbic acid hybrid antioxidant based cationic amphiphile for gene delivery: Design, synthesis and transfection.
- Author
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Muripiti, Venkanna, Brijesh, Lohchania, Rachamalla, Hari Krishnareddy, Marepally, Srujan Kumar, Banerjee, Rajkumar, and Patri, Srilakshmi V.
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VITAMIN C , *AMPHIPHILES , *ANTIOXIDANTS , *CATIONIC lipids , *BIOLOGICAL systems , *CHEMICAL synthesis - Abstract
Graphical abstract Highlights • Design and synthesis of an efficient anti-oxidant lipid for gene delivery. • Hybrid of two natural anti-oxidants. • Two and half fold better potent than the commercial lipid lipofectamine 2000 in delivering pDNA. • Least cytotoxic especially neuro cell lines. • Serum compatible. • Can be exploited as a delivering system for treating ROS related diseases such as malignancy, brain stroke etc. Abstract 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 in N14-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. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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