Polyethylenimine-Grafted Polyamidoamine Conjugates for Gene Delivery with High Efficiency and Low Cytotoxicity

Tae-Hun Kim; Ho Won Seo; Jin Han; Kyung Soo Ko; Joon Sig Choi

Macromolecular Research, Vol.22, No.7, 757-764, July, 2014

DOI10.1007/s13233-014-2108-8 Export Citation

Polyethylenimine-Grafted Polyamidoamine Conjugates for Gene Delivery with High Efficiency and Low Cytotoxicity

Tae-Hun Kim¹, Ho Won Seo², Jin Han³, Kyung Soo Ko^{4, †}, and Joon Sig Choi^{1, 5, †}

¹Department of Biochemistry, Chungnam National University, Daejeon, 305-764, Korea
²Graduate School of Nanoscience and Technology (GSNT), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Korea
³Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, 614-735, Korea
⁴Department of Internal Medicine, Sanggye Paik Hospital, Cardiovascular and Metabolic Disease Center, Inje University, Seoul, 139-707, Korea
⁵Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Korea

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Hyperbranched polymers, polyamidoamine-methyl acrylate-polyethylenimine-ethylenediamine (PMPE) conjugates, were synthesized as a novel non-viral gene carrier based on polyamidoamine. These PMPE derivatives exhibit high transfection efficiency and low cytotoxicity. We linked methyl acrylate (MA) on polyamidoamine (PAMAM) and grafted PEI onto the PAMAM-MA, and then grafted ethylenediamine (EDA) onto the PAMAM-MA-PEI. Four polymers, PAMAM G2-MA-PEI 800-EDA, PAMAM G3-MA-PEI 800-EDA and PAMAM G2-MA-PEI 2000-EDA, PAMAM G3-MA-PEI 2000-EDA, were synthesized and characterized by 1H NMR. PMPE was shown to interact with and condense plasmid DNA effectively to form 149-220 nm polyplexes with 34-43 mV of zeta potentials at weight ratio as 4:1 (polymer/plasmid DNA). Cytotoxicity of PMPE/pDNA complexes was lower than that of polyethylenimine (PEI) 25 kDa/pDNA complexes for all concentration ranges. In 293 and HeLa cells, PMPE/pDNA complexes showed much higher gene transfection efficiency than PAMAM. These results suggested that PMPE is an attractive novel vector for non-viral gene delivery system.

Keywords:PAMAM dendrimer;polyethylenimine;polyplexes;nanoparticles;transfection.

[References]

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[Referenced By]

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

[2] Cavazzana-Calvo M, Hacein-Bey S, De Saint Basile G, Gross F, Yvon E, Nusbaum P, Science, 288, 669 (2000)

[3] Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Lancet, 369, 2097 (2007)

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

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

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

[7] Godbey WT, Wu KK, Mikos AG, J. Control. Release, 60, 149 (1999)

[8] Tomalia DA, Naylor AM, Goddard WA, Angew. Chem. Int. Ed. Eng., 29, 138 (1990)

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

[10] Haensler J, Szoka FC, Bioconjug. Chem., 4, 372 (1993)

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

[12] Kolhatkar RB, Kitchens KM, Swaan PW, Ghandehari H, Bioconjug. Chem., 18, 2054 (2007)

[13] Son SJ, Yu GS, Choe YH, Kim YJ, Lee EJ, Park JS, Choi JS, Bull. Korea Chem. Soc., 34, 579 (2013)

[14] Yu GS, Bae YM, Kim JY, Han J, Ko KS, Choi JS, Macromol. Res., 20(11), 1156 (2012)

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

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

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

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

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

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

[21] Kim SW, Ogawa T, Tabata Y, Nishimura I, J. Biomed. Mater. Res. A, 71, 308 (2004)

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

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

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

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

[26] Navarro G, Maiwald G, Haase R, Rogach AL, Wagner E, de Ilarduya CT, Ogris M, J. Control. Release, 17, 99 (2010)

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