α-Tocopherol-ascorbic acid hybrid antioxidant based cationic amphiphile for gene delivery: Design,synthesis and transfection |
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| Institution: | 1. National Institute of Technology, Warangal 506004, Telangana, India;2. Centre for Stem Cell Research, Vellore 632002, Tamil Nadu, India;3. Division of Lipid Science and Technology, Indian Institute of Chemical Technology, Hyderabad 500607, Telangana, India;1. Escola de Química, Universidade Federal do Rio de Janeiro, CEP 22941 909 Rio de Janeiro, Brazil;2. Laboratório de Biocatálise e Síntese Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-909 Rio de Janeiro, RJ, Brazil;1. Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain;2. Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos s/n, 29071 Málaga, Spain;1. Dipartimento di Scienze Fisiche e Chimiche, Università degli Studi dell’Aquila, Via Vetoio 10, 67010, Coppito, AQ, Italy;2. Dipartimento di Chimica, Università di Roma “Sapienza”, Piazzale Aldo Moro 5, 00185, Roma, Italy;3. Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Esfera UAB, Campus UAB s/n, E-08193, Cerdanyola del Vallès, Spain;4. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Campus Universitari de Bellaterra, E-08193, Cerdanyola, Spain |
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| 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 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. |
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| Keywords: | Ascorbic acid Transfection Gene delivery Cationic liposomes Antioxidant |
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