Effective delivery of anti-miRNA DNA oligonucleotides by functionalized gold nanoparticles |
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Authors: | Kim Jae-Hong Yeom Ji-Hyun Ko Jeong-Jae Han Min Su Lee Kangseok Na Soon-Young Bae Jeehyeon |
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Institution: | a Department of Pharmacy, College of Pharmacy, CHA University, Seongnam 463-836, Republic of Korea b Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea c Department of Chemistry, Chung-Ang University, Seoul 156-756, Republic of Korea |
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Abstract: | MicroRNAs (miRNAs) are gaining recognition as essential regulators involved in many biological processes, and they are emerging as therapeutic targets for treating disease. Here, we introduce a method for effective delivery of anti-miRNA oligonucleotides (AMOs) using functionalized gold nanoparticles (AuNPs). To demonstrate the ability of AMOs to silence miRNA, we selected miR-29b, which is known to downregulate myeloid cell leukemia-1 (MCL-1), a factor responsible for promoting cell survival. We first generated AuNPs coated with cargo DNA, which was then coupled to complementary DNA linked to an antisense miR-29b sequence. When the AuNPs were delivered into HeLa cells, MCL-1 protein and mRNA levels were increased significantly. Furthermore, apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was inhibited, proving that AMOs targeting miR-29b were effectively delivered by our innovative AuNP. In addition, we provided evidence that AuNP could deliver other AMOs against miR-21 into two independent cell lines, KGN and 293T, suggesting that the AuNP conjugates can be versatile for any AMO and cell type. |
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Keywords: | Anti-microRNA oligonucleotides (AMOs) Gold nanoparticles miR-29 MCL-1 |
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