Intracellular delivery of recombinant proteins via gold nanoparticle-DNA aptamer composites is independent of the protein physicochemical properties and cell type

Ji-Hyun Yeom; Minju Joo; Boeun Lee; Keun P. Kim; Nam-Chul Ha; Yoonkyung Park; Jeehyeon Bae; Kangseok Lee

Journal of Industrial and Engineering Chemistry, Vol.45, 5-10, January, 2017

DOI10.1016/j.jiec.2016.09.043 Export Citation

Intracellular delivery of recombinant proteins via gold nanoparticle-DNA aptamer composites is independent of the protein physicochemical properties and cell type

Ji-Hyun Yeom, Minju Joo, Boeun Lee, Keun P. Kim, Nam-Chul Ha¹, Yoonkyung Park², Jeehyeon Bae^{3, †}, and Kangseok Lee^†

Department of Life Science, Chung-Ang University, Seoul 06974, Republic of Korea
¹Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea
²Department of Biomedical Science, Chosun University, Gwangju 61452, Republic of Korea
³School of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea

E-mail:,

Here, we report that the gold nanoparticle.DNA aptamer (AuNP.Apt) conjugate-based system can efficiently deliver recombinant proteins into mammalian cells in a manner independent of their size, isoelectric point, and cellular localization. Additionally, AuNP.Apt system-assisted protein delivery can be effective on primary and stem cells, indicating that its use is not limited to fast-dividing cells. We further show that the intravenously administered AuNP.Apt system can deliver proteins into rat organs. Our findings show that this system can serve as a simple, efficient, and versatile platform for the delivery of recombinant proteins into mammalian living systems.

Keywords:DNA aptamer;Gold nanoparticle;Protein delivery;Intravenous delivery

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[1] Torchilin V, Drug Discov. Today Technol., 5, e95 (2008)

[2] Yu M, Wu J, Shi J, Farokhzad OC, J. Control. Release, 240, 24 (2016)

[3] Gu Z, Biswas A, Zhao M, Tang Y, Chem. Soc. Rev., 40, 3638 (2011)

[4] Green I, Christison R, Voyce CJ, Bundell KR, Lindsay MA, Trends Pharmacol. Sci., 24, 213 (2003)

[5] Brown LR, Expert Opin. Drug Deliv., 2, 29 (2005)

[6] Patel LN, Zaro JL, Shen WC, Pharm. Res., 24, 1977 (2007)

[7] Weeks BS, Lieberman DM, Johnson B, Roque E, Green M, Loewenstein P, Oldfield EH, Kleinman HK, J. Neurosci. Res., 42, 34 (1995)

[8] Zeng F, Lee H, Allen C, Bioconjugate Chem., 17, 399 (2006)

[9] Gindy ME, Ji SX, Hoye TR, Panagiotopoulos AZ, Prud'homme RK, Biomacromolecules, 9(10), 2705 (2008)

[10] Jule E, Nagasaki Y, Kataoka K, Bioconjugate Chem., 14, 177 (2003)

[11] Hussey SL, Peterson BR, J. Am. Chem. Soc., 124(22), 6265 (2002)

[12] Hill AB, Chen M, Chen CK, Pfeifer BA, Jones CH, Trends Biotechnol., 34, 91 (2016)

[13] Ryou SM, Yeom JH, Kang HJ, Won M, Kim JS, Lee B, Seong MJ, Ha NC, Bae J, Lee K, J. Control. Release, 196, 287 (2014)

[14] McKeague M, Derosa MC, J. Nucleic Acids, 2012, 748913 (2012)

[15] Rosi NL, Giljohann DA, Thaxton CS, Lytton-Jean AK, Han MS, Mirkin CA, Science, 312, 1027 (2006)

[16] Kim JH, Jang HH, Ryou SM, Kim S, Bae J, Lee K, Han MS, Chem. Commun., 46, 4151 (2010)

[17] Kim D, Jeong YY, Jon S, ACS Nano, 4, 3689 (2010)

[18] Lee JK, Park SC, Hahm KS, Park Y, Biomaterials, 35, 1025 (2014)

[19] Kim D, Yeom JH, Lee B, Lee K, Bae J, Rhee S, Biochem. Biophys. Res. Commun., 464(2), 392 (2015)

[20] Yeom JH, Lee B, Kim D, Lee JK, Kim S, Bae J, Park Y, Lee K, Biomaterials, 104, 43 (2016)

[21] Jamieson S, Butzow R, Andersson N, Alexiadis M, Unkila-Kallio L, Heikinheimo M, Fuller PJ, Anttonen M, Mod. Pathol., 23, 1477 (2010)

[22] Cho WS, Cho M, Jeong J, Choi M, Cho HY, Han BS, Kim SH, Kim HO, Lim YT, Chung BH, Jeong J, Toxicol. Appl. Pharmacol., 236, 16 (2009)

[23] Wojnicki M, Luty-Blocho M, Bednarski M, Dudek M, Knutelska J, Sapa J, Zygmunt M, Nowak G, Fitzner K, Pharmacol. Rep., 65, 1033 (2013)

[24] Jung YS, Lee SJ, Lee SH, Chung JY, Jung YJ, Hwang SH, Ha NC, Park BJ, Cell Cycle, 12, 2277 (2013)

[25] Lee M, Yeom JH, Sim SH, Ahn S, Lee K, Curr. Microbiol., 58(4), 349 (2009)

[26] Sim SH, Yeom JH, Shin C, Song WS, Shin E, Kim HM, Cha CJ, Han SH, Ha NC, Kim SW, Hahn Y, Bae J, Lee K, Mol. Microbiol., 75, 413 (2010)

[27] Park M, Shin E, Won M, Kim JH, Go H, Kim HL, Ko JJ, Lee K, Bae J, Mol. Endocrinol., 24, 1024 (2010)

[28] Liou GG, Chang HY, Lin CS, Lin-Chao S, J. Biol. Chem., 277, 41157 (2002)