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Issue 2, 2020
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Targeted delivery of Chil3/Chil4 siRNA to alveolar macrophages using ternary complexes composed of HMG and oligoarginine micelles

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Abstract

Cell-type-specific genes involved in disease can be effective therapeutic targets; therefore, the development of a cell-type-specific gene delivery system is essential. In this study, targeted delivery of Chil3 and Chil4 siRNA to activated macrophages was developed using a ligand called high mobility group (HMG) and oligoarginine (OR) micelles. HMG binds to TLR4 and RAGE located on the surface of activated macrophages. Since HMG is positively charged, it binds to the negatively charged siRNA by charge interaction. However, the stable formation of the siRNA/HMG complex requires an additional molecule to act as a carrier. In this study, OR micelles were used as the carrier. Gel retardation assays showed that siRNA, HMG, and OR micelles formed stable siRNA/HMG/OR micelle ternary complexes. In vitro transfection showed that the ternary complexes selectively delivered siRNA to TLR4 expressing macrophages. In addition, intratracheal administration of siRNA/HMG/OR ternary complexes delivered Chil3 and Chil4 siRNA specifically to alveolar macrophages. Furthermore, the siRNA that was delivered using ternary complexes reduced Chil3 and Chil4 expression and suppressed the symptoms of asthma, such as airway inflammation and mucin secretion.

Graphical abstract: Targeted delivery of Chil3/Chil4 siRNA to alveolar macrophages using ternary complexes composed of HMG and oligoarginine micelles

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Supplementary files

Article information


Submitted
26 Jul 2019
Accepted
26 Nov 2019
First published
27 Nov 2019

Nanoscale, 2020,12, 933-943
Article type
Paper

Targeted delivery of Chil3/Chil4 siRNA to alveolar macrophages using ternary complexes composed of HMG and oligoarginine micelles

M. Choi, H. Jeong, S. Kim, M. Kim, M. Lee and T. Rhim, Nanoscale, 2020, 12, 933
DOI: 10.1039/C9NR06382J

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