title: Effective delivery of anti-miRNA DNA oligonucleotides by functionalized gold nanoparticles.
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.
authors.affiliation: Department of Pharmacy, College of Pharmacy, CHA University, Seongnam 463-836, Republic of Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Yeom
authors.forename: Jeong-Jae
authors.initials: JJ
authors.lastname: Ko
authors.forename: Min Su
authors.initials: MS
authors.lastname: Han
authors.forename: Kangseok
authors.initials: K
authors.lastname: Lee
authors.forename: Soon-Young
authors.initials: SY
authors.lastname: Na
authors.forename: Jeehyeon
authors.initials: J
authors.lastname: Bae
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D058726:Nanoconjugates / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D058726:Nanoconjugates; D016376:Oligonucleotides, Antisense; C114487:PDCD4 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D006046:Gold