Abstract
Cationic lipids 1, 2, and 3, based on hydrophobic cholesterol linked to L-lysine, L-histidine or L-arginine, respectively, were designed and tested as gene delivery vectors. Physicochemical and biological properties of all liposomes and lipoplexes were evaluated, including lipid-DNA interactions, size, morphology, zeta potential, acid-base buffering capability, protection of DNA from DNase I digestion, and cytotoxity. The efficiency of luciferase gene transfection of lipoplexes 1–3 was compared with that of commercial dioleoyl-trimethylammonium propane (DOTAP) and polyethyleneimine (PEI) in 293T cells and HepG2 cells with or without poly(ethylene glycol) PEG stabilizer. The complexation and protection of DNA of liposome 3 was the strongest among the three liposomes. The efficiency of gene transfection of liposomes 1–3 was two-to threefold higher than that of PEI and/or DOTAP in 293T cells. Liposomes 1 and 3 in PEG as stabilizer showed sixfold higher transfection efficiency than that of PEI and/or DOTAP, whereas liposome 2 showed very low transfection efficiency. In HepG2 cells, the transfection efficiency of all the cationic liposomes was much lower than that of DOTAP. In conclusion, lipids 1–3 were efficient and non-toxic gene vectors; the headgroup of cationic lipids and the stabilizer of liposome formulation had an important influence on gene transfection.
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Akinc, A., Thomas, M., Klibanov, A. M., and Langer, R., Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis. J. Gene Med., 7, 657–663 (2005).
Budker, V, Gurevich, V, Hagstrom, J. E., Bortzov, F., and Wolff, J. A., pH-sensitive, cationic liposomes: A new synthetic virus-like vector. Nature Biot., 14, 760–764 (1996).
Chabaud, P., Camplo, M., Payet, D., Serin, G., Moreau, L., Barthelemy, P., and Grinstaff, M. W., Cationic nucleoside lipids for gene delivery. Bioconj. Chem., 17, 466–472 (2006).
Choi, J. S., Lee, E. J., Jang, H. S., and Park, J. S., New cationic liposomes for gene transfer into mammalian cells with high efficiency and low toxicity. Bioconj. Chem., 12, 108–113 (2001).
Choosakoonkriang, S., Lobo, B. A., Koe, G. S., Koe, J. G., and Middaugh, C. R., Biophysical characterization of PEI/DNA complexes. J. Pharm. Sci., 92, 1710–1722 (2003).
Ciani, L., Ristori, S., Calamai, L., and Martini, G., DOTAP/DOPE and DC-Chol/DOPE lipoplexes for gene delivery: zeta potential measurements and electron spin resonance spectra. BBA-Biom., 1664, 70–79 (2004).
De Laporte, L, Rea, J. C., and Shea, L. D., Design of modular non-viral gene therapy vectors. Biomaterials, 27, 947–954 (2006).
Ewert, K. K., Evans, H. M., Bouxsein, N. F., and Safinya, C. R., Dendritic cationic lipids with highly charged headgroups for efficient gene delivery. Bioconj. Chem., 17, 877–888 (2006).
Gershon, H, Ghirlando, R., Guttman, S. B., and Minsky, A., Mode of formation and structural features of DNA cationic liposome complexes used for transfection. Biochem., 32, 7143–7151 (1993).
Heyes, J. A., Niculescu-Duvaz, D., Cooper, R. G., and Springer, C. J., Synthesis of novel cationic lipids: Effect of structural modification on the efficiency of gene transfer. J. Med. Chem., 45, 99–114 (2002).
Karmali, P. P. and Chaudhuri, A., Cationic Liposomes as non-viral carriers of gene medicines: Resolved issues, open questions, and future promises. Med. Res. Rev., 27, 696–722 (2007).
Karmali, P. P., Kumar, V. V., and Chaudhuri, A., Design, syntheses and in vitro gene delivery efficacies of novel mono-, di-and trilysinated cationic lipids: A structure-activity investigation. J. Med. Chem., 47, 2123–2132 (2004).
Karmali, P. P., Majeti, B. K., Sreedhar, B., and Chaudhuri, A., In vitro gene transfer efficacies and serum compatibility profiles of novel mono-, di-, and tri-histidinylated cationic transfection lipids: A structure-activity investigation. Bioconj. Chem., 17, 159–171 (2006).
Keller, M., Harbottle, R. P., Perouzel, E., Colin, M., Shah, L., Rahim, A., and Vaysse, L., Bergau., Nuclear localisation sequence templated nonviral gene delivery vectors: Investigation of intracellular trafficking events, of LMD and LD vector systems. Chembiochem, 4, 286–298 (2003).
Kim, T. I., Baek, J. U., Bai, C. Z., and Park, J. S., Arginine-conjugated polypropylenimine dendrimer as a non-toxic and efficient gene delivery carrier. Biomaterials, 28, 2061–2067 (2007).
Kumar, V. V., Pichon, C., Refregiers, M., Guerin, B., Midoux, P., and Chaudhuri, A., Single histidine residue in head-group region is sufficient to impart remarkable gene transfection properties to cationic lipids: evidence for histidine-mediated membrane fusion at acidic pH. Gene Ther., 10, 1206–1215 (2003).
Martin, B., Sainlos, M., Aissaoui, A., Oudrhiri, N., Hauchecorne, M., Vigneron, J. P., Lehn, J. M., and Lehn, P., The design of cationic lipids for gene delivery. Curr. Pharm. Des., 11, 375–394 (2005)
Miller A. D., Cationic liposomes for gene therapy. Angew. Chem. Int. Ed., 37, 1769–1785 (1998).
Okuda, T., Sugiyama, A., Niidome, T., and Aoyagi, H., Characters of dendritic poly((L)-lysine) analogues with the terminal lysines replaced with arginines and histidines as gene carriers in vitro. Biomaterials, 25, 537–544 (2004).
Okuda, T., Kawakami, S., Akimoto, N., Niidome, T., Yamashita, F., and Hashida, M., PEGylated lysine dendrimers for tumor-selective targeting after intravenous injection in tumor-bearing mice. J Contr. Rel., 116, 330–336 (2006).
Reimer, D. L., Zhang Y. P., Kong S, Wheeler J. J., Graham R. W., and Bally M. B., Formation of novel hydrophobic complexes between cationic lipids and plasmid DNA. Biochem. 34, 12877–12883 (1995).
Rossi J. J., Medicine: A cholesterol connection in RNAi. Nature, 432, 155–156 (2004).
Safinya, C. R., Structures of lipid-DNA complexes: supramolecular assembly and gene delivery. Curr. Opin. Struct. Bio., 11, 440–448 (2001).
Shigeta, K., Kawakami, S., Higuchi, Y., Okuda, T., Yagi, H., Yamashita, F., and Hashida, M., Novel histidine-conjugated galactosylated cationic liposomes for efficient hepatocyte-selective gene transfer in human hepatoma HepG2 cells. J. Contr. Rel., 118, 262–270 (2007).
Simons, K. and Ikonen, E., Cell biology — How cells handle cholesterol. Science, 290, 1721–1726 (2000).
Singh, R. S., Goncalves, C., Sandrin, P., Pichon, C., Midoux, P., and Chaudhuri, A., On the gene delivery efficacies of pH-sensitive cationic lipids via endosomal protonation: a chemical biology investigation. Chem. & Bio., 11, 713–723 (2004).
Sochanik, A., Kaida, I., Mitrus, I., Rajca, A., and Szala, S., A new cholesterol derivative suitable for transfecting certain type of cells in the presence of 10% serum. Canc. Gene Ther., 7, 513–520 (2000).
Solodin, I., Brown, C. S., Bruno, M. S., Chow, C. Y., Jang, E. H., Debs, R. J., and Heath, T. D., A novel series of amphiphilic imidazolinium compounds for in-vitro and in-vivo gene delivery. Biochem., 34, 13537–13544 (1995).
Verma, S. K., Mani, P., Sharma, N. R., Krishnan, A., Kumar, V. V., Reddy, B. S., Chaudhuri, A., Roy, R. P., and Sarkar, D. P., Histidylated lipid-modified Sendai viral envelopes mediate enhanced membrane fusion and potentiate targeted gene delivery. J. Bio, Chem., 280, 35399–35409 (2005).
Vigneron, J. P., Oudrhiri, N., Fauquet, M., Vergely, L., Bradley, J. C., Basseville, M., Lehn, P., and Lehn, J. M., Guanidinium-cholesterol cationic lipids: Efficient vectors for the transfection of eukaryotic cells. Proc. Nat. Acad. Sci. U.S.A., 93, 9682–9686 (1996).
Wieland, J. A., Houchin-Ray, T. L., and Shea, L. D., Non-viral vector delivery from PEG-hyaluronic acid hydrogels. J. Contr. Rel., 120, 233–241 (2007).
Wiethoff, C. M. and Middaugh, C. R., Barriers to nonviral gene delivery. J. Pharm. Sci., 92, 203–217 (2003).
Zelphati, O., Nguyen, C., Ferrari, M., Felgner, J., Tsai, Y., and Felgner, P.L., Stable and monodisperse lipoplex formulations for gene delivery. Gene Ther., 5, 1272–1282 (1998).
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Li, L., Nie, Y., Zhu, R. et al. Preparation and gene delivery of alkaline amino acids-based cationic liposomes. Arch. Pharm. Res. 31, 924–931 (2008). https://doi.org/10.1007/s12272-001-1248-8
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DOI: https://doi.org/10.1007/s12272-001-1248-8