title: Combined Delivery of Temozolomide and Anti-miR221 PNA Using Mesoporous Silica Nanoparticles Induces Apoptosis in Resistant Glioma Cells.
abstract: Mesoporous silica nanoparticles (MSNPs), 100 nm in size, incorporating a Cy5 fluorophore within the silica framework, are synthesized and loaded with the anti-cancer drug temozolomide (TMZ), used in the treatment of gliomas. The surface of the particles is then decorated, using electrostatic interactions, with a polyarginine-peptide nucleic acid (R8-PNA) conjugate targeting the miR221 microRNA. The multi-functional nanosystem thus obtained is rapidly internalized into glioma C6 or T98G cells. The anti-miR activity of the PNA is retained, as confirmed by reverse transcription polymerase chain reaction (RT-PCR) measurements and induction of apoptosis is observed in temozolomide-resistant cell lines. The TMZ-loaded MSNPs show an enhanced pro-apoptotic effect, and the combined effect of TMZ and R8-PNA in the MSNPs shows the most effective induction of apoptosis (70.9% of apoptotic cells) thus far achieved in the temozolomide-resistant T98G cell line.
authors.affiliation: Institut de science et d'ingénierie supramoléculaire (ISIS) & icFRC, Université de Strasbourg & CNRS, 8 Rue Gaspard Monge, Strasbourg, 67000, France.|Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, Parma, 43124, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertucci
authors.affiliation: Institut de science et d'ingénierie supramoléculaire (ISIS) & icFRC, Université de Strasbourg & CNRS, 8 Rue Gaspard Monge, Strasbourg, 67000, France.
authors.forename: Eko Adi
authors.initials: EA
authors.lastname: Prasetyanto
authors.affiliation: Institut de science et d'ingénierie supramoléculaire (ISIS) & icFRC, Université de Strasbourg & CNRS, 8 Rue Gaspard Monge, Strasbourg, 67000, France.
authors.forename: Dedy
authors.initials: D
authors.lastname: Septiadi
authors.affiliation: Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, Parma, 43124, Italy.
authors.forename: Alex
authors.initials: A
authors.lastname: Manicardi
authors.affiliation: Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Via Luigi Borsari 46, Ferrara, 44121, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brognara
authors.affiliation: Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Via Luigi Borsari 46, Ferrara, 44121, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.affiliation: Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, Parma, 43124, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Corradini
authors.affiliation: Institut de science et d'ingénierie supramoléculaire (ISIS) & icFRC, Université de Strasbourg & CNRS, 8 Rue Gaspard Monge, Strasbourg, 67000, France.
authors.forename: Luisa
authors.initials: L
authors.lastname: De Cola
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D020135:Peptide Nucleic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D016062:Porosity; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry* / Q000627:therapeutic use; D000077204:Temozolomide
chemical_list: D003606:Dacarbazine; D004338:Drug Combinations; D035683:MicroRNAs; D020135:Peptide Nucleic Acids; D010455:Peptides; D012822:Silicon Dioxide; D000077204:Temozolomide; C525709:MIR221, human; C015462:polyarginine
keywords: drug resistance; mesoporous silica; microRNA; nanomaterials; nanomedicine