Cellular Delivery of siRNA Using Poly(2-dimethylaminoethyl methacrylate)- Functionalized Graphene Oxide Nano-Wrap

Jung Eun Lee; Kyuri Lee; Jeong A Nam; Aesun Kim; So Young Lee; Min Sang Lee; Nak Won Kim; Yue Yin; Ji Won Park; Sung Young Park; Ji Hoon Jeong

Macromolecular Research, Vol.26, No.12, 1115-1122, December, 2018

DOI10.1007/s13233-019-7017-4 Export Citation

Cellular Delivery of siRNA Using Poly(2-dimethylaminoethyl methacrylate)- Functionalized Graphene Oxide Nano-Wrap

Jung Eun Lee, Kyuri Lee, Jeong A Nam¹, Aesun Kim, So Young Lee¹, Min Sang Lee, Nak Won Kim, Yue Yin, Ji Won Park, Sung Young Park^{1, †}, and Ji Hoon Jeong^†

School of Pharmacy, Sungkyunkwan University, Suwon 16149, Korea
¹Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 27469, Korea

E-mail:,

Despite its high therapeutic potential, the use of siRNA has still been limited mostly due to the lack of a proper delivery system. Small number of charges and inflexible structure of siRNA are the major factors that affect cellular delivery efficiency of conventional lipid and polymeric carriers. In this study, we synthesized a 2-dimensional (2D) carrier for siRNA using a facile method to functionalize and stabilize the surface of graphene oxide (GO) with catechol-derivatized poly(2-dimethylaminoethyl methacrylate) (C-p(DMAEMA)). The resulting GO/C-p(DMAEMA) can interact with siRNA on the flexible 2D surface of the GO, wrapping up siRNA molecules by folding to form a dim sum-like nano structure. GO/C-p(DMAEMA) demonstrated significantly improved cellular uptake and enhanced gene silencing efficiency in the presence of serum protein, compared to unmodified GO and bPEI 25 kDa.

Keywords:non-viral gene delivery;siRNA;graphene oxide;nano-wrap;dim sum-like structure

[References]

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Pai SI, Lin YY, Macaes B, Meneshian A, Hung CF, Wu TC, Gene Ther., 13, 464 (2006)
Kim DH, Rossi JJ, Nat. Rev. Genet., 8, 173 (2007)
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Bumcrot D, Manoharan M, Koteliansky V, Sah DW, Sah, Nat. Chem. Biol., 2, 711 (2006)
Jeong JH, Kim SW, Park TG, Prog. Polym. Sci., 32, 1239 (2007)
Jeong JH, Mok H, Oh YK, Park TG, Bioconjug. Chem., 20, 5 (2009)
Jeong JH, Christensen LV, Yockman JW, Zhong Z, Engbersen JF, Kim WJ, Feijen J, Kim SW, Biomaterials, 28, 1912 (2007)
Sarisozen C, Pan J, Dutta I, Torchilin VP, J. Pharm. Investig., 47, 37 (2017)
Mok H, Lee SH, Park JW, Park TG, Nat. Mater., 9(3), 272 (2010)
Lee SY, Huh MS, Lee S, Lee SJ, Chung H, Park JH, Oh YK, Choi K, Kim K, Kwon IC, J. Control. Release, 141, 339 (2010)
Bao H, Pan Y, Ping Y, Sahoo NG, Wu T, Li L, Li J, Gan LH, Small, 7, 1569 (2011)
Kim H, Lee D, Kim J, Kim TI, Kim WJ, ACS Nano, 7, 6735 (2013)
Jang H, Kim YK, Kwon HM, Yeo WS, Kim DE, Min DH, Angew. Chem.-Int. Edit. Engl., 49, 5703 (2010)
Liu Z, Robinson JT, Sun XM, Dai HJ, J. Am. Chem. Soc., 130(33), 10876 (2008)
Kim H, Namgung R, Singha K, Oh IK, Kim WJ, Bioconjug. Chem., 22, 2558 (2011)
Kim H, Kim WJ, Small, 10, 117 (2014)
Pei S, Cheng HM, Carbon, 50, 3210 (2012)
Robinson JT, Tabakman SM, Liang YY, Wang HL, Casalongue HS, Vinh D, Dai HJ, J. Am. Chem. Soc., 133(17), 6825 (2011)
Hu SH, Chen YW, Hung WT, Chen IW, Chen SY, Adv. Mater., 24(13), 1748 (2012)
Liu S, Zeng TH, Hofmann M, Burcombe E, Wei J, Jiang R, Kong J, Chen Y, ACS Nano, 5, 6971 (2011)
Lee H, Dellatore SM, Miller WM, Messersmith PB, Science, 318, 426 (2007)
Oh YJ, Cho IH, Lee H, Park KJ, Lee H, Park SY, Chem. Commun., 48, 11895 (2012)
Lee BP, Huang K, Nunalee FN, Shull K, Messersmith PB, J. Biomater. Sci.-Polym. Ed., 15, 449 (2004)
Kang SM, Park S, Kim D, Park SY, Ruoff RS, Lee H, Adv. Funct. Mater., 21(1), 108 (2011)
Hummers SW, Offeman RE, J. Am. Chem. Soc., 80, 1339 (1958)
Dreyer DR, Park S, Bielawski CW, Ruoff RS, Chem. Soc. Rev., 39, 228 (2010)
Taktak F, Yildiz M, Sert H, Soykan C, J. Macromol. Sci. Part A, 52, 39 (2014)
Mosaiab T, Jeong CJ, Shin GJ, Choi KH, Lee SK, Lee I, In I, Park SY, Mater. Sci. Eng. C: Mater. Biol. Appl., 33, 3786 (2013)
Park TG, Jeong JH, Kim SW, Adv. Drug Deliv. Rev., 58, 467 (2006)
Mok H, Lee SH, Park JW, Park TG, Nat. Mater., 9(3), 272 (2010)
Kim WJ, Kim SW, Pharm. Res., 26, 657 (2009)
Lee SY, Huh MS, Lee S, Lee SJ, Chung H, Park JH, Oh YK, Choi K, Kim K, Kwon IC, J. Control. Release, 141, 339 (2010)
Lee H, Jeong JH, Park TG, J. Control. Release, 79, 283 (2002)

[Referenced By]

[1] Hannon GJ, Rossi JJ, Nature, 431, 371 (2004)

[2] Pai SI, Lin YY, Macaes B, Meneshian A, Hung CF, Wu TC, Gene Ther., 13, 464 (2006)

[3] Kim DH, Rossi JJ, Nat. Rev. Genet., 8, 173 (2007)

[4] Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Tuschl KWT, Nature, 411, 494 (2001)

[5] Bumcrot D, Manoharan M, Koteliansky V, Sah DW, Sah, Nat. Chem. Biol., 2, 711 (2006)

[6] Jeong JH, Kim SW, Park TG, Prog. Polym. Sci., 32, 1239 (2007)

[7] Jeong JH, Mok H, Oh YK, Park TG, Bioconjug. Chem., 20, 5 (2009)

[8] Jeong JH, Christensen LV, Yockman JW, Zhong Z, Engbersen JF, Kim WJ, Feijen J, Kim SW, Biomaterials, 28, 1912 (2007)

[9] Sarisozen C, Pan J, Dutta I, Torchilin VP, J. Pharm. Investig., 47, 37 (2017)

[10] Mok H, Lee SH, Park JW, Park TG, Nat. Mater., 9(3), 272 (2010)

[11] Lee SY, Huh MS, Lee S, Lee SJ, Chung H, Park JH, Oh YK, Choi K, Kim K, Kwon IC, J. Control. Release, 141, 339 (2010)

[12] Bao H, Pan Y, Ping Y, Sahoo NG, Wu T, Li L, Li J, Gan LH, Small, 7, 1569 (2011)

[13] Kim H, Lee D, Kim J, Kim TI, Kim WJ, ACS Nano, 7, 6735 (2013)

[14] Jang H, Kim YK, Kwon HM, Yeo WS, Kim DE, Min DH, Angew. Chem.-Int. Edit. Engl., 49, 5703 (2010)

[15] Liu Z, Robinson JT, Sun XM, Dai HJ, J. Am. Chem. Soc., 130(33), 10876 (2008)

[16] Kim H, Namgung R, Singha K, Oh IK, Kim WJ, Bioconjug. Chem., 22, 2558 (2011)

[17] Kim H, Kim WJ, Small, 10, 117 (2014)

[18] Pei S, Cheng HM, Carbon, 50, 3210 (2012)

[19] Robinson JT, Tabakman SM, Liang YY, Wang HL, Casalongue HS, Vinh D, Dai HJ, J. Am. Chem. Soc., 133(17), 6825 (2011)

[20] Hu SH, Chen YW, Hung WT, Chen IW, Chen SY, Adv. Mater., 24(13), 1748 (2012)

[21] Liu S, Zeng TH, Hofmann M, Burcombe E, Wei J, Jiang R, Kong J, Chen Y, ACS Nano, 5, 6971 (2011)

[22] Lee H, Dellatore SM, Miller WM, Messersmith PB, Science, 318, 426 (2007)

[23] Oh YJ, Cho IH, Lee H, Park KJ, Lee H, Park SY, Chem. Commun., 48, 11895 (2012)

[24] Lee BP, Huang K, Nunalee FN, Shull K, Messersmith PB, J. Biomater. Sci.-Polym. Ed., 15, 449 (2004)

[25] Kang SM, Park S, Kim D, Park SY, Ruoff RS, Lee H, Adv. Funct. Mater., 21(1), 108 (2011)

[26] Hummers SW, Offeman RE, J. Am. Chem. Soc., 80, 1339 (1958)

[27] Dreyer DR, Park S, Bielawski CW, Ruoff RS, Chem. Soc. Rev., 39, 228 (2010)

[28] Taktak F, Yildiz M, Sert H, Soykan C, J. Macromol. Sci. Part A, 52, 39 (2014)

[29] Mosaiab T, Jeong CJ, Shin GJ, Choi KH, Lee SK, Lee I, In I, Park SY, Mater. Sci. Eng. C: Mater. Biol. Appl., 33, 3786 (2013)

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

[31] Mok H, Lee SH, Park JW, Park TG, Nat. Mater., 9(3), 272 (2010)

[32] Kim WJ, Kim SW, Pharm. Res., 26, 657 (2009)

[33] Lee SY, Huh MS, Lee S, Lee SJ, Chung H, Park JH, Oh YK, Choi K, Kim K, Kwon IC, J. Control. Release, 141, 339 (2010)

[34] Lee H, Jeong JH, Park TG, J. Control. Release, 79, 283 (2002)