PMID- 21739990 OWN - NLM STAT- MEDLINE DCOM- 20111227 LR - 20131121 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 5 IP - 8 DP - 2011 Aug 23 TI - Target-specific gene silencing of layer-by-layer assembled gold-cysteamine/siRNA/PEI/HA nanocomplex. PG - 6138-47 LID - 10.1021/nn2017793 [doi] AB - Target-specific intracellular delivery of small interfering RNA (siRNA) is regarded as one of the most important technologies for the development of siRNA therapeutics. In this work, a cysteamine modified gold nanoparticles (AuCM)/siRNA/polyethyleneimine (PEI)/hyaluronic acid (HA) complex was successfully developed using a layer-by-layer method for target-specific intracellular delivery of siRNA by HA receptor mediated endocytosis. Atomic force microscopic and zeta potential analyses confirmed the formation of a AuCM/siRNA/PEI/HA complex having a particle size of ca. 37.3 nm and a negative surface charge of ca. -12 mV. With a negligible cytotoxicity, AuCM/siRNA/PEI/HA complex showed an excellent target-specific gene silencing efficiency of ca. 70% in the presence of 50 vol % serum, which was statistically much higher than that of siRNA/Lipofectamine 2000 complex. In the competitive binding tests with free HA, dark-field bioimaging and inductively coupled plasma-atomic emission spectroscopy confirmed the target-specific intracellular delivery of AuCM/siRNA/PEI/HA complex to B16F1 cells with HA receptors. Moreover, the systemic delivery of AuCM/siRNA/PEI/HA complex using apolipoprotein B (ApoB) siRNA as a model drug resulted in a significantly reduced ApoB mRNA level in the liver tissue. Taken together, AuCM/siRNA/PEI/HA complex was thought to be developed as target-specific siRNA therapeutics for the systemic treatment of various liver diseases. CI - (c) 2011 American Chemical Society FAU - Lee, Min-Young AU - Lee MY AD - Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Korea. FAU - Park, Sang-Jun AU - Park SJ FAU - Park, Kitae AU - Park K FAU - Kim, Ki Su AU - Kim KS FAU - Lee, Hwiwon AU - Lee H FAU - Hahn, Sei Kwang AU - Hahn SK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110708 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 0 (Apolipoproteins B) RN - 0 (Drug Carriers) RN - 0 (RNA, Small Interfering) RN - 5UX2SD1KE2 (Cysteamine) RN - 7440-57-5 (Gold) RN - 9002-98-6 (Polyethyleneimine) RN - 9004-61-9 (Hyaluronic Acid) SB - IM MH - Animals MH - Apolipoproteins B/deficiency/genetics MH - Base Sequence MH - Cell Line, Tumor MH - Cysteamine/*chemistry MH - Drug Carriers/chemistry/metabolism MH - Endocytosis MH - *Gene Silencing MH - Gold/*chemistry MH - Hyaluronic Acid/*chemistry MH - Intracellular Space/metabolism MH - Liver Diseases/genetics/metabolism/therapy MH - Mice MH - Models, Molecular MH - Molecular Conformation MH - Molecular Imaging MH - Nanostructures/chemistry MH - Nanotechnology/*methods MH - Polyethyleneimine/*chemistry MH - RNA, Small Interfering/*chemistry/genetics EDAT- 2011/07/12 06:00 MHDA- 2011/12/28 06:00 CRDT- 2011/07/12 06:00 PHST- 2011/07/12 06:00 [entrez] PHST- 2011/07/12 06:00 [pubmed] PHST- 2011/12/28 06:00 [medline] AID - 10.1021/nn2017793 [doi] PST - ppublish SO - ACS Nano. 2011 Aug 23;5(8):6138-47. doi: 10.1021/nn2017793. Epub 2011 Jul 8.