title: Single-Vehicular Delivery of Antagomir and Small Molecules to Inhibit miR-122 Function in Hepatocellular Carcinoma Cells by using "Smart" Mesoporous Silica Nanoparticles.
abstract: MicroRNAs (miRNAs) regulate a variety of biological processes. The liver-specific, highly abundant miR-122 is implicated in many human diseases including cancer. Its inhibition has been found to result in a dramatic loss in the ability of Hepatitis C virus (HCV) to infect host cells. Both antisense technology and small molecules have been used to independently inhibit endogenous miR-122 function, but not in combination. Intracellular stability, efficient delivery, hydrophobicity, and controlled release are some of the current challenges associated with these novel therapeutic methods. Reported herein is the first single-vehicular system, based on mesoporous silica nanoparticles (MSNs), for simultaneous cellular delivery of miR-122 antagomir and small molecule inhibitors. The controlled release of both types of inhibitors depends on the expression levels of endogenous miR-122, thus enabling these drug-loaded MSNs to achieve combination inhibition of its targeted mRNAs in Huh7 cells.
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao.
authors.forename: Changmin
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao.
authors.forename: Linghui
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Uttamchandani
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543 (Singapore) http://staff.science.nus.edu.sg/∼syao. chmyaosq@nus.edu.sg.
authors.forename: Shao Q
authors.initials: SQ
authors.lastname: Yao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D053758:Nanoparticles; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012822:Silicon Dioxide
keywords: bioimaging; drug delivery; mesoporous silica nanoparticles; microRNA; small-molecule inhibitor