title: Tailored Nanoparticle Codelivery of antimiR-21 and antimiR-10b Augments Glioblastoma Cell Kill by Temozolomide: Toward a "Personalized" Anti-microRNA Therapy.
abstract: Glioblastoma remains an aggressive brain malignancy with poor prognosis despite advances in multimodal therapy that include standard use of Temozolomide. MicroRNA-21 (miR-21) and microRNA-10b (miR-10b) are oncomiRs overexpressed in glioblastoma, promoting many aspects of cancer biology. We hypothesized that PLGA nanoparticles carrying antisense miR-21 (antimiR-21) and antisense miR-10b (antimiR-10b) might beneficially knockdown endogenous miR-21 and miR-10b function and reprogram cells prior to Temozolomide treatment. PLGA nanoparticles were effective in intracellular delivery of encapsulated oligonucleotides. Concentrations of delivered antimiR-21 and antimiR-10b were optimized and specifically tailored to copy numbers of intracellular endogenous microRNAs. Coinhibition of miR-21 and miR-10b significantly reduced the number of viable cells (by 24%; p < 0.01) and increased (2.9-fold) cell cycle arrest at G2/M phase upon Temozolomide treatment in U87 MG cells. Cell-tailored nanoparticle-assisted concurrent silencing of miR-21 and miR-10b prior to Temozolomide treatment is an effective molecular therapeutic strategy in cell culture, warranting the need for further studies prior to future in vivo "personalized" medicine applications.
authors: 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: Jeyarama S
authors: JS
authors: Ananta
authors: 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: Ramasamy
authors: R
authors: Paulmurugan
authors: 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: Tarik F
authors: TF
authors: Massoud
mesh_terms: D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D060888:Real-Time Polymerase Chain Reaction; D000077204:Temozolomide
chemical_list: C547183:MIRN10 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003606:Dacarbazine; D000077204:Temozolomide
keywords: PLGA nanoparticle; anti-microRNA therapy; antisense miR-10b; antisense miR-21; glioblastoma; microRNA-10b; microRNA-21; personalized medicine