期刊
NANOSCALE
卷 12, 期 2, 页码 933-943出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c9nr06382j
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资金
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [NRF-2014R1A2A2A01006740, NRF-2017R1A2B4012007, NRF-2012M3A9D1054451]
- National Research Foundation of Korea [5199990514440, 2012M3A9D1054451, 22A20130011095] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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