title: Nanoparticle-Delivered Antisense MicroRNA-21 Enhances the Effects of Temozolomide on Glioblastoma Cells.
abstract: Glioblastoma (GBM) generally exhibits high IC50 values for its standard drug treatment, temozolomide (TMZ). MicroRNA-21 (miR-21) is an oncomiR overexpressed in GBM, thus controlling important aspects of glioma biology. We hypothesized that PLGA nanoparticles carrying antisense miR-21 to glioblastoma cells might beneficially knock down endogenous miR-21 prior to TMZ treatment. PLGA nanoparticles encapsulating antisense miR-21 were effective in intracellular delivery and sustained silencing (p < 0.01) of miR-21 function in U87 MG, LN229, and T98G cells. Prior antisense miR-21 delivery significantly reduced the number of viable cells (p < 0.001), and increased (1.6-fold) cell cycle arrest at G2/M phase upon TMZ treatment in U87 MG cells. There was overexpression of the miR-21 target genes PTEN (by 67%) and caspase-3 (by 15%) upon cotreatment. This promising PLGA nanoparticle-based platform for antisense miR-21 delivery to GBM is an effective cotherapeutic strategy in cell culture, warranting the need for further studies prior to future clinical translation.
authors.affiliation: Laboratory of Experimental and Molecular Neuroimaging, Molecular Imaging Program at Stanford (MIPS), and Bio-X Program, Stanford University School of Medicine , Stanford, California 94305-5427, United States.
authors.forename: Jeyarama S
authors.initials: JS
authors.lastname: Ananta
authors.affiliation: Laboratory of Experimental and Molecular Neuroimaging, Molecular Imaging Program at Stanford (MIPS), and Bio-X Program, Stanford University School of Medicine , Stanford, California 94305-5427, United States.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Paulmurugan
authors.affiliation: Laboratory of Experimental and Molecular Neuroimaging, Molecular Imaging Program at Stanford (MIPS), and Bio-X Program, Stanford University School of Medicine , Stanford, California 94305-5427, United States.
authors.forename: Tarik F
authors.initials: TF
authors.lastname: Massoud
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D016375:Antisense Elements (Genetics) / Q000235:genetics*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics; D005910:Glioma / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D053758:Nanoparticles / Q000008:administration & dosage*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D016375:Antisense Elements (Genetics); C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D003606:Dacarbazine; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3; D000077204:Temozolomide
keywords: GBM; PLGA; antisense miR-21; microRNA-21; nanoparticle; temozolomide