Novel hyperbranched polyethyleneimine conjugate as an efficient non-viral gene delivery vector

Tae-Hun Kim; Hye Choi; Gwang Sig Yu; Jeil Lee; Joon Sig Choi

Macromolecular Research, Vol.21, No.10, 1097-1104, October, 2013

DOI10.1007/s13233-013-1154-y Export Citation

Novel hyperbranched polyethyleneimine conjugate as an efficient non-viral gene delivery vector

Tae-Hun Kim¹, Hye Choi¹, Gwang Sig Yu¹, Jeil Lee², and Joon Sig Choi^{1, 2, †}

¹Department of Biochemistry, Chungnam National University, Daejeon, 305-764, Korea
²Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Korea

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In this study, we developed polyethyleneimine-methyl acrylate-polyethyleneimine (PMP) conjugate as a novel, non-viral gene carrier based on low molecular weight polyethyleneimine, and proved PMP derivative exhibit high gene transfection efficiency and low toxicity. We linked methyl acrylate (MA) on polyethyleneimine (PEI) and then grafted PEI onto the PEI-MA. The synthesized PMP was characterized by 1H NMR and FTIR. When added to DNA solution, PMP condensed with DNA at weight ratios over 1:1 (polymer:DNA) to form 96?108 nm polyplexes with 37 mV of zeta potential. In cytotoxicity assay, PMP turned out less toxic than PEI 25 kDa. In vitro transfection assays showed that the gene transfection of PMP/pDNA complexes was similar or slightly higher than that of the PEI 25 kDa/pDNA complexes in 293, HeLa, and HepG2 cells. Our data suggest that PMP-based gene delivery system is economical, effective, and biocompatible, and it may be a promising gene delivery vector for gene therapies.

Keywords:polyethylenimine;hyperbranched;gene delivery;polyplex;transfection

[References]

Friedmann T, Roblin R, Science, 175, 949 (1972)
Kaspar BK, Llado J, Sherkat N, Rothstein JD, Gage FH, Science, 301, 839 (2003)
Cavazzana-Calvo M, Hacein-Bey S, De Saint Basile G, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P, Le Deist F, Fischer A, Science, 288, 669 (2000)
Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ, Lancet, 369, 2097 (2007)
Li S, Huang L, Gene Ther., 7, 31 (2000)
Tiera MJ, Winnik FM, Fernandes JC, Curr. Gene Ther., 6, 59 (2006)
Niven R, Pearlman R, Wedeking T, Mackeigan J, Noker P, Simpson-Herren L, Smith JG, J. Pharm. Sci., 87, 1292 (1998)
Guillot-Nieckowski M, Eisler S, Diederich F, New J. Chem., 31, 1111 (2007)
Verma IM, Somia N, Nature, 389(6648), 239 (1997)
Miller AD, Curr. Top. Microbiol. Immunol., 158, 1 (1992)
Luo D, Saltzman WM, Nat. Biotechnol., 18, 33 (2000)
Han SO, Mahato RI, Sung YK, Kim SW, Mol. Ther., 2, 302 (2000)
Lee M, Kim SW, Pharm. News, 9, 407 (2002)
Mintzer MA, Simanek EE, Chem. Rev., 109(2), 259 (2009)
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)
Nimesh S, Goyal A, Pawar V, Jayaraman S, Kumar P, Chandra R, Singh Y, Gupta KC, J. Control. Release, 110, 457 (2006)
Klemm AR, Young D, Lloyd JB, Biochem. Pharmacol., 56, 41 (1998)
Labat-Moleur F, Steffan AM, Brisson C, Perron H, Feugeas O, Fustenberger P, Oberling F, Brambilla E, Behr JP, Gene Ther., 3, 1010 (1996)
Mislick KA, Baldeschwieler JD, Proc. Natl. Acad. Sci. U.S.A., 93, 12349 (1996)
Behr JP, Chimia, 51, 34 (1997)
Sonawane ND, Szoka FC, Verkman AS, J. Biol. Chem., 278, 44826 (2003)
Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP, Proc. Natl. Acad. Sci. U.S.A., 92, 7297 (1995)
Fischer D, Bieber T, Li Y, Elsasser HP, Kissel T, Pharm. Res., 16, 1273 (1999)
Godbey WT, Wu KK, Mikos AG, Biomaterials, 22, 471 (2001)
Choi JS, Nam K, Park JY, Kim JB, Lee JK, Park JS, J. Control. Release, 99, 445 (2004)
Xu DM, Yao SD, Liu YB, Sheng KL, Hong J, Gong PJ, Dong L, Int. J. Pharm., 338, 291 (2007)
Xianga S, Tong H, Shi Q, Fernandes JC, Jin T, Dai K, Zhang X, J. Control. Release, 158, 371 (2011)
Pack DW, Hoffman AS, Pun S, Stayton PS, Nat. Rev. Drug Discov., 4, 581 (2005)
Park TG, Jeong JH, Kim SW, Adv. Drug Deliv. Rev., 58, 467 (2006)
Lv H, Zhang S, Wang B, Cui S, Yan J, J. Control. Release, 114, 100 (2006)

[1] Friedmann T, Roblin R, Science, 175, 949 (1972)

[2] Kaspar BK, Llado J, Sherkat N, Rothstein JD, Gage FH, Science, 301, 839 (2003)

[3] Cavazzana-Calvo M, Hacein-Bey S, De Saint Basile G, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P, Le Deist F, Fischer A, Science, 288, 669 (2000)

[4] Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ, Lancet, 369, 2097 (2007)

[5] Li S, Huang L, Gene Ther., 7, 31 (2000)

[6] Tiera MJ, Winnik FM, Fernandes JC, Curr. Gene Ther., 6, 59 (2006)

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

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

[9] Verma IM, Somia N, Nature, 389(6648), 239 (1997)

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

[11] Luo D, Saltzman WM, Nat. Biotechnol., 18, 33 (2000)

[12] Han SO, Mahato RI, Sung YK, Kim SW, Mol. Ther., 2, 302 (2000)

[13] Lee M, Kim SW, Pharm. News, 9, 407 (2002)

[14] Mintzer MA, Simanek EE, Chem. Rev., 109(2), 259 (2009)

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

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

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

[18] Klemm AR, Young D, Lloyd JB, Biochem. Pharmacol., 56, 41 (1998)

[19] Labat-Moleur F, Steffan AM, Brisson C, Perron H, Feugeas O, Fustenberger P, Oberling F, Brambilla E, Behr JP, Gene Ther., 3, 1010 (1996)

[20] Mislick KA, Baldeschwieler JD, Proc. Natl. Acad. Sci. U.S.A., 93, 12349 (1996)

[21] Behr JP, Chimia, 51, 34 (1997)

[22] Sonawane ND, Szoka FC, Verkman AS, J. Biol. Chem., 278, 44826 (2003)

[23] Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP, Proc. Natl. Acad. Sci. U.S.A., 92, 7297 (1995)

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

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

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

[27] Xu DM, Yao SD, Liu YB, Sheng KL, Hong J, Gong PJ, Dong L, Int. J. Pharm., 338, 291 (2007)

[28] Xianga S, Tong H, Shi Q, Fernandes JC, Jin T, Dai K, Zhang X, J. Control. Release, 158, 371 (2011)

[29] Pack DW, Hoffman AS, Pun S, Stayton PS, Nat. Rev. Drug Discov., 4, 581 (2005)

[30] Park TG, Jeong JH, Kim SW, Adv. Drug Deliv. Rev., 58, 467 (2006)

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