TY - JOUR
T1 - Cationic liquid crystalline nanoparticles for the delivery of synthetic RNAi-based therapeutics
AU - Gentile, Emanuela
AU - Oba, Taro
AU - Lin, Jing
AU - Shao, Ruping
AU - Meng, Feng
AU - Cao, Xiaobo
AU - Lin, Heather Y.
AU - Mourad, Majidi
AU - Pataer, Apar
AU - Baladandayuthapani, Veerabhadran
AU - Cai, Dong
AU - Roth, Jack A.
AU - Ji, Lin
N1 - Funding Information:
A kind acknowledgment to E. Dondossola, PhD for her intellectual and scientific contributions, I. Kumar Mishra for performing the Nanoparticles Tracking Analysis, R. Romero Aburto, PhD for helping with Dynamic Light Scattering Analysis and D. S. Keener for her informatics support.This study is partially supported by NIH/NCI Lung SPORE grant 5P50CA070907 and R01CA176568, a CPRIT grant, and an MD Anderson Cancer Center Moonshot Program Grant. Supported by the NIH/NCI under award number P30CA016672: The Flow Cytometry and Cellular Imaging (FCCI) Core Facility, The High Resolution Electron Microscopy Facility (HREMF). VB and HYL were also supported by the UT MD Anderson Cancer Center core grant P30CA016672.
Publisher Copyright:
© Gentile et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.18632/oncotarget.18421
DO - 10.18632/oncotarget.18421
M3 - Article
AN - SCOPUS:85024362838
VL - 8
SP - 48222
EP - 48239
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 29
ER -