Exploring membrane permeability of Tomatidine to enhance lipid mediated nucleic acid transfections |
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Authors: | Vignesh K Rangasami Brijesh Lohchania Chandrashekhar Voshavar Harikrishna R Rachamalla Rajkumar Banerjee Ashish Dhayani Saravanabhavan Thangavel Praveen K Vemula Srujan Marepally |
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Institution: | 1. Centre for Stem Cell Research, Christian Medical College Campus, Bagayam, Vellore 632002, India;2. BioSatva Technologies, Golnaka, Hyderabad 500013, India;3. Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India;4. Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK-post, Bellary Road, Bengaluru 560065, India;5. The School of Chemical and Biotechnology, SASTRA University, Thirumalaisamudram, Thanjavur-613401,Tamil Nadu, India |
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Abstract: | Intracellular delivery of nucleic acids is one of the critical steps in the transfections. Prior findings demonstrated various strategies including membrane fusion, endosomal escape for the efficient cytoplasmic delivery. In our continuing efforts to improve the nucleic acids transfections, we harnessed cell permeable properties of Tomatidine (T), a steroidal alkaloid abundantly found in green tomatoes for maximizing intracellular delivery of lipoplexes. We doped Tomatidine into liposomes of cationic lipid with amide linker (A) from our lipid library. Six liposomal formulations (AT) of Lipid A (1?mM) with varying concentrations of Tomatidine (0–1?mM) were prepared and evaluated for their transfection efficacies. Owing to its signature characteristic of cell membrane permeability, Tomatidine modulated endocytosis process, enhanced the intracellular delivery of the lipoplexes, and in turn increased the transfection efficacy of cationic liposomes. Our findings provide ‘proof of concept’ for enhancing transfections in gene delivery applications with Tomatidine in cationic liposomal formulations. These findings can be further applied in lipid mediated gene therapy and drug delivery applications. |
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Keywords: | Tomatidine Amide linker lipid Liposome Transfection Cell permeability Endocytosis |
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