Cationic liquid crystalline nanoparticles for the delivery of synthetic RNAi-based therapeutics

Emanuela Gentile, Taro Oba, Jing Lin, Ruping Shao, Feng Meng, Xiaobo Cao, Heather Y. Lin, Majidi Mourad, Apar Pataer, Veerabhadran Baladandayuthapani, Dong Cai, Jack A. Roth, Lin Ji

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

RNA interference (RNAi)-based therapeutics have been used to silence the expression of targeted pathological genes. Small interfering RNA (siRNAs) and microRNA (miRNAs) inhibitor have performed this function. However, short halflife, poor cellular uptake, and nonspecific distribution of small RNAs call for the development of novel delivery systems to facilitate the use of RNAi. We developed a novel cationic liquid crystalline nanoparticle (CLCN) to efficiently deliver synthetic siRNAs and miRNAs. CLCNs were prepared by using high-speed homogenization and assembled with synthetic siRNA or miRNA molecules in nuclease-free water to create CLCN/siRNA or miRNA complexes. The homogeneous and stable CLCNs and CLCNsiRNA complexes were about 100 nm in diameter, with positively charged surfaces. CLCNs are nontoxic and are taken up by human cells though endocytosis. Significant inhibition of gene expression was detected in transiently transfected lung cancer H1299 cells treated with CLCNs/anti-GFP complexes 24 hours after transfection. Biodistribution analysis showed that the CLCNs and CLCNs-RNAi complexes were successfully delivered to various organs and into the subcutaneous human lung cancer H1299 tumor xenografts in mice 24 hours after systemic administration. These results suggest that CLCNs are a unique and advanced delivery system capable of protecting RNAi from degradation and of efficiently delivering RNAi in vitro and in vivo.

Original languageEnglish
Pages (from-to)48222-48239
Number of pages18
JournalOncotarget
Volume8
Issue number29
DOIs
Publication statusPublished - Jan 1 2017

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RNA Interference
Nanoparticles
MicroRNAs
Small Interfering RNA
Lung Neoplasms
Therapeutics
RNA Stability
Endocytosis
Heterografts
Transfection
Half-Life
RNA
Gene Expression
Water
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Cationic liquid crystalline nanoparticles for the delivery of synthetic RNAi-based therapeutics. / Gentile, Emanuela; Oba, Taro; Lin, Jing; Shao, Ruping; Meng, Feng; Cao, Xiaobo; Lin, Heather Y.; Mourad, Majidi; Pataer, Apar; Baladandayuthapani, Veerabhadran; Cai, Dong; Roth, Jack A.; Ji, Lin.

In: Oncotarget, Vol. 8, No. 29, 01.01.2017, p. 48222-48239.

Research output: Contribution to journalArticle

Gentile, E, Oba, T, Lin, J, Shao, R, Meng, F, Cao, X, Lin, HY, Mourad, M, Pataer, A, Baladandayuthapani, V, Cai, D, Roth, JA & Ji, L 2017, 'Cationic liquid crystalline nanoparticles for the delivery of synthetic RNAi-based therapeutics', Oncotarget, vol. 8, no. 29, pp. 48222-48239. https://doi.org/10.18632/oncotarget.18421
Gentile, Emanuela ; Oba, Taro ; Lin, Jing ; Shao, Ruping ; Meng, Feng ; Cao, Xiaobo ; Lin, Heather Y. ; Mourad, Majidi ; Pataer, Apar ; Baladandayuthapani, Veerabhadran ; Cai, Dong ; Roth, Jack A. ; Ji, Lin. / Cationic liquid crystalline nanoparticles for the delivery of synthetic RNAi-based therapeutics. In: Oncotarget. 2017 ; Vol. 8, No. 29. pp. 48222-48239.
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