Surface modification of RNA nanoparticles by ionic interaction for efficient cellular uptake

Hyunsu Jeon; Sangwoo Han; Hyejin Kim; Jong Bum Lee

Journal of Industrial and Engineering Chemistry, Vol.70, 87-93, February, 2019

DOI10.1016/j.jiec.2018.10.013 Export Citation

Surface modification of RNA nanoparticles by ionic interaction for efficient cellular uptake

Hyunsu Jeon, Sangwoo Han, Hyejin Kim, and Jong Bum Lee^†

Department of Chemical Engineering, University of Seoul, 163 Seoulsiripdaero, Dongdaemungu, Seoul 02504, Republic of Korea

E-mail:

Small interference RNA (siRNA) delivery has gained much attention for specific regulation of target protein via RNA interference. However, it has been challenged by inherent instability of naked RNA. To address this issue, a variety of siRNA delivery methods have been developed. The synthesis of RNA nanoparticles (RNPs) by complementary rolling circle transcription (cRCT) has been introduced as a novel route for siRNA delivery, because of the enhanced stability in serum condition and the suitable size for enhanced permeation and retention (EPR) effect. However, RNPs are negatively charged due to the innate structure of RNA, resulting in an inefficient cellular uptake without using transfection agents. In this paper, we report a simple surface modification method of RNP with calcium ion. Calcium-layered RNA nanoparticles (CaRNPs) were generated and used to demonstrate enhanced efficiency of siRNA delivery to HeLa cells in vitro. The results revealed that this simple approach could enhance the cellular uptake efficiency of RNPs in contrast to the naked RNP. Moreover, this method is also applicable for other types of RNAs such as messenger RNA (mRNA), microRNA (miRNA), or single guide RNA (sgRNA), which will greatly enhance therapeutic potential of RNPs.

Keywords:Calcium coated RNA nanoparticle (CaRNP);Complementary rolling circle transcription;(cRCT);siRNA delivery system;Enhanced cellular uptake

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[11] Kim HA, Nam K, Kim SW, Biomaterials, 35, 7543 (2014)

[12] Park DH, Cho J, Kwon OJ, Yun CO, Angew. Chem.-Int. Edit., 55, 4582 (2016)

[13] Liong M, Lu J, Kovochich M, Xia T, Ruehm SG, Nel AE, Tamanoi F, Zink JI, ACS Nano, 2, 889 (2008)

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

[15] Gilleron J, Querbes W, Zeigerer A, Borodovsky A, Marsico G, Schubert U, et al., Nat. Biotechnol., 31, 638 (2013)

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[18] Lee JB, Hong J, Bonner DK, Poon Z, Hammond PT, Nat. Mater., 11(4), 316 (2012)

[19] Han D, Park Y, Nam H, Lee JB, Chem. Commun., 50, 11665 (2014)

[20] Kim H, Jeong J, Kim D, Kwak G, Kim SH, Lee JB, Adv. Sci., 4, 160052 (2017)

[21] Han S, Kim H, Lee JB, Sci. Rep., 7, 10005 (2017)

[22] Kim H, Kim D, Jeong J, Jeon H, Lee JB, Polymers, 10, 589 (2018)

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[29] Nichols JW, Bae YH, J. Control. Release, 190, 451 (2014)