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Combined Delivery of Temozolomide and Anti‐miR221 PNA Using Mesoporous Silica Nanoparticles Induces Apoptosis in Resistant Glioma Cells
Author(s) -
Bertucci Alessandro,
Prasetyanto Eko Adi,
Septiadi Dedy,
Manicardi Alex,
Brognara Eleonora,
Gambari Roberto,
Corradini Roberto,
De Cola Luisa
Publication year - 2015
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201500540
Subject(s) - temozolomide , mesoporous silica , apoptosis , glioma , peptide nucleic acid , chemistry , fluorophore , cell culture , materials science , biophysics , cancer research , nucleic acid , mesoporous material , biochemistry , fluorescence , biology , genetics , catalysis , physics , quantum mechanics
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.