Polyethylenimine-poly(amidoamine) dendrimer modified with l -arginines as an efficient gene delivery vector

Nan Young Ahn; Tae-Hun Kim; Su Jeong Song; Jeong-Mi Moon; Tai Hwan Ha; Joon Sig Choi

Macromolecular Research, Vol.23, No.8, 726-733, August, 2015

DOI10.1007/s13233-015-3101-6 Export Citation

Polyethylenimine-poly(amidoamine) dendrimer modified with l -arginines as an efficient gene delivery vector

Nan Young Ahn¹, Tae-Hun Kim¹, Su Jeong Song¹, Jeong-Mi Moon¹, Tai Hwan Ha^{2, †}, and Joon Sig Choi^{1, 3, †}

¹Department of Biochemistry, Chungnam National University, Daejeon, 305-764, Korea
²Future Biotechnology Research Division, Korea Research Institute of Bioscience and Biotechnology (KRIBB),, 125 Gwahak-ro, Daejeon, 305-806, Korea
³Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Korea

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In this study, we synthesized polyethylenimine-polyamidoamine-arginine dendritic polymers (PPRs) as vectors for gene delivery. Four polymers, polyethylenimine-polyamidoamine generation 1 (PP1), PP2, PP1-arginine (PP1R), and PP2-arginine (PP2R), were synthesized and confirmed by 1H NMR. PPRs were shown to interact with and condense plasmid DNA effectively to form 171-179 nm polyplexes with 30-32 mV of zeta potentials at weight ratio 4:1 (polymer:plasmid DNA). Cytotoxicity of PPRs/pDNA complexes was lower than that of polyethylenimine (PEI) 25 kDa/pDNA complexes for all concentration ranges tested. In 293 cells, PP1R/pDNA complexes showed higher gene transfection efficiency than PEI 25 kDa. These results suggest that PPR could be promising dendritic gene carriers for gene therapy.

Keywords:dendrimer;polyethylenimine;poly(amidoamine);L-arginine;nanoparticles

[References]

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Miller AD, Curr. Top. Microbiol. Immunol., 158, 1 (1992)
Lee M, Kim SW, Parmaceutical News, 9, 407 (2002)
Kircheis R, Wightman L, Wagner E, Adv. Drug Deliv. Rev., 53, 341 (2001)
Kunath K, Harpe AV, Fischer D, Petersen H, Bickel U, Voigt K, Kissel T, J. Control. Release, 89, 113 (2003)
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Fischer D, Bieber T, Li Y, Elsasser HP, Kissel T, Pharm. Res., 16, 1273 (1999)
Godbey T, Wu KK, Mikos AG, J. Biomed. Mater. Res., 45, 268 (1999)
Godbey WT, Wu KK, Mikos AG, Biomaterials, 22, 471 (2001)
Remy JS, Abdallah B, Zanta MA, Boussif O, Behr JP, Demeneix B, Adv. Drug Deliv. Rev., 30, 85 (1998)
Guillot-Nieckowski M, Eisler S, Diederich F, New J. Chem., 31, 1111 (2007)
Freeman AW, Frechet JMJ, in Dendrimers and Other Dendritic Polymers, Frechet JMJ, Tomalia DA, Eds., John Wiley & Sons, Chichester, 2001, pp 91-101.
Smith DK, Curr. Top. Med. Chem., 8, 1187 (2008)
Haensler J, Szoka FC, Bioconjugate Chem., 4, 372 (1993)
Braun CS, Vetro JA, Tomalia DA, Koe GS, Koe JG, Middaugh CR, J. Pharm. Sci., 94, 423 (2005)
Josephson L, Tung CH, Moore A, Weissleder R, Bioconjugate Chem., 10, 186 (1999)
Suk JS, Suh J, Choy K, Lai SK, Fu J, Hanes J, Biomaterials, 27, 5143 (2006)
Choi JS, Nam K, Park JY, Kim JB, Lee JK, Park JS, J. Control. Release, 99, 445 (2004)
Lee MJ, Cho SS, You JR, Lee Y, Kang BD, Choi JS, Park JW, Suh YL, Kim JA, Kim DK, Park JS, Gene Ther., 9, 859 (2002)
Win KY, Feng SS, Biomaterials, 26, 2713 (2005)
Moghimi SM, Hunter AC, Murray JC, Pharm. Rev., 53, 283 (2001)
Mahatos RI, Rolland A, Tomlinson E, Pharm. Rev., 14, 853 (1997)
Guy J, Drabek D, Antoniou M, Mol. Biotechnol., 3, 237 (1995)
Lv H, Zhang S, Wang B, Cui S, Yan J, J. Control. Release, 114, 100 (2006)
Richard JP, Melikov K, Vives E, Ramos C, Verbeure B, Gait MJ, Chernomordik LV, Lebleu B, J. Biol. Chem., 278, 585 (2003)
Fischer R, Kohler K, Fotin-Mleczek M, Brock R, J. Biol. Chem., 279, 12625 (2004)
Fittipaldi A, Ferrari A, Zoppe M, Arcangeli C, Pellegrini V, Beltram F, Giacca M, J. Biol. Chem., 278, 34141 (2003)
Kim TI, Baek JU, Yoon JK, Choi JS, Kim K, Park JS, Bioconjugate Chem., 18, 309 (2007)

[Referenced By]

[1] Niven R, Pearlman R, Wedeking T, Mackeigan J, Noker P, Simpson-Herren L, Smith JG, J. Pharm. Sci., 87, 1292 (1998)

[2] Miller AD, Curr. Top. Microbiol. Immunol., 158, 1 (1992)

[3] Lee M, Kim SW, Parmaceutical News, 9, 407 (2002)

[4] Kircheis R, Wightman L, Wagner E, Adv. Drug Deliv. Rev., 53, 341 (2001)

[5] Kunath K, Harpe AV, Fischer D, Petersen H, Bickel U, Voigt K, Kissel T, J. Control. Release, 89, 113 (2003)

[6] Nimesh S, Goyal A, Pawar V, Jayaraman S, Kumar P, Chandra R, Singh Y, Gupta KC, J. Control. Release, 110, 457 (2006)

[7] Fischer D, Bieber T, Li Y, Elsasser HP, Kissel T, Pharm. Res., 16, 1273 (1999)

[8] Godbey T, Wu KK, Mikos AG, J. Biomed. Mater. Res., 45, 268 (1999)

[9] Godbey WT, Wu KK, Mikos AG, Biomaterials, 22, 471 (2001)

[10] Remy JS, Abdallah B, Zanta MA, Boussif O, Behr JP, Demeneix B, Adv. Drug Deliv. Rev., 30, 85 (1998)

[11] Guillot-Nieckowski M, Eisler S, Diederich F, New J. Chem., 31, 1111 (2007)

[12] Freeman AW, Frechet JMJ, in Dendrimers and Other Dendritic Polymers, Frechet JMJ, Tomalia DA, Eds., John Wiley & Sons, Chichester, 2001, pp 91-101.

[13] Smith DK, Curr. Top. Med. Chem., 8, 1187 (2008)

[14] Haensler J, Szoka FC, Bioconjugate Chem., 4, 372 (1993)

[15] Braun CS, Vetro JA, Tomalia DA, Koe GS, Koe JG, Middaugh CR, J. Pharm. Sci., 94, 423 (2005)

[16] Josephson L, Tung CH, Moore A, Weissleder R, Bioconjugate Chem., 10, 186 (1999)

[17] Suk JS, Suh J, Choy K, Lai SK, Fu J, Hanes J, Biomaterials, 27, 5143 (2006)

[18] Choi JS, Nam K, Park JY, Kim JB, Lee JK, Park JS, J. Control. Release, 99, 445 (2004)

[19] Lee MJ, Cho SS, You JR, Lee Y, Kang BD, Choi JS, Park JW, Suh YL, Kim JA, Kim DK, Park JS, Gene Ther., 9, 859 (2002)

[20] Win KY, Feng SS, Biomaterials, 26, 2713 (2005)

[21] Moghimi SM, Hunter AC, Murray JC, Pharm. Rev., 53, 283 (2001)

[22] Mahatos RI, Rolland A, Tomlinson E, Pharm. Rev., 14, 853 (1997)

[23] Guy J, Drabek D, Antoniou M, Mol. Biotechnol., 3, 237 (1995)

[24] Lv H, Zhang S, Wang B, Cui S, Yan J, J. Control. Release, 114, 100 (2006)

[25] Richard JP, Melikov K, Vives E, Ramos C, Verbeure B, Gait MJ, Chernomordik LV, Lebleu B, J. Biol. Chem., 278, 585 (2003)

[26] Fischer R, Kohler K, Fotin-Mleczek M, Brock R, J. Biol. Chem., 279, 12625 (2004)

[27] Fittipaldi A, Ferrari A, Zoppe M, Arcangeli C, Pellegrini V, Beltram F, Giacca M, J. Biol. Chem., 278, 34141 (2003)

[28] Kim TI, Baek JU, Yoon JK, Choi JS, Kim K, Park JS, Bioconjugate Chem., 18, 309 (2007)