PMID- 32865449 OWN - NLM STAT- MEDLINE DCOM- 20210820 LR - 20210820 IS - 1557-7465 (Electronic) IS - 1079-9907 (Linking) VI - 40 IP - 10 DP - 2020 Oct TI - Spherical Gold Nanoparticles: Small Interfering RNA Delivery in Regulation of the Tumor Necrosis Factor-Alpha Gene Expression. PG - 490-496 LID - 10.1089/jir.2020.0090 [doi] AB - Proinflammatory cytokines are signaling molecules that are expelled from immune cells like macrophages and other types of cells. Tumor necrosis factor-alpha (TNF-alpha) is overexpressed during inflammation caused by inflammatory diseases. Therefore, the regulation of TNF-alpha has a key role in inflammation. The use and target delivery of small interfering RNAs (siRNAs) provide many effectual treatment benefits in the regulation of gene expression in cells. In this study, we used siRNA nanoparticle conjugates in the regulation of gene expression and inflammation. We first prepared safe fusion ribonucleic acid interference carrier, spherical nucleic acid nanoparticle conjugates (SNA-NCs), to enhance the perforation of siRNA into the macrophages and their ability to target TNF-alpha gene regulation. Furthermore, the suppression of the TNF-alpha gene was monitored after curing macrophages by SNA-NCs. Gene expression was carried out by real-time polymerase chain reaction in cells and the levels of TNF-alpha were investigated by the enzyme-linked immunosorbent assay (ELISA) method. This study indicated that the SNA-NCs were safe and very stable. TNF-alpha siRNA could significantly regulate gene expression in cells to form SNA-NCs. The results indicated that TNF-alpha gene expression downregulated to 93.40% +/- 1.45%, 66.06% +/- 0.95%, and 35.76% +/- 1.09% in the presence of 0.1, 1, and 10 nM siRNA, respectively. The proliferation of macrophages and subsequently expression of TNF-alpha were significant for the formation of inflammation. These findings showed that the use of SNA-NC siRNA might ameliorate the inflammatory disease by suppression of gene expression and functional activity of macrophage generation. FAU - Hosseinzadeh, Leila AU - Hosseinzadeh L AD - Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. FAU - Nemati, Houshang AU - Nemati H AD - Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. FAU - Nemati, Narges AU - Nemati N AD - Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. FAU - Sadeghi, Masoud AU - Sadeghi M AD - Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200828 PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Necrosis Factor-alpha) RN - 7440-57-5 (Gold) SB - IM MH - Animals MH - Cell Survival MH - Down-Regulation MH - *Gene Expression Regulation MH - *Gold MH - *Metal Nanoparticles MH - Mice MH - RAW 264.7 Cells MH - *RNA, Small Interfering/administration & dosage MH - Tumor Necrosis Factor-alpha/biosynthesis/*genetics OTO - NOTNLM OT - TNF-alpha OT - inflammation OT - macrophages OT - nanoparticles OT - siRNA EDAT- 2020/09/01 06:00 MHDA- 2021/08/21 06:00 CRDT- 2020/09/01 06:00 PHST- 2020/09/01 06:00 [pubmed] PHST- 2021/08/21 06:00 [medline] PHST- 2020/09/01 06:00 [entrez] AID - 10.1089/jir.2020.0090 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2020 Oct;40(10):490-496. doi: 10.1089/jir.2020.0090. Epub 2020 Aug 28.