Combined Delivery of Temozolomide and Anti-miR221 PNA Using Mesoporous Silica Nanoparticles Induces Apoptosis in Resistant Glioma Cells

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. Multifunctional mesoporous silica nanoparticles (MSNPs) are extremely efficient for glioblastoma treatment, combining both excellent drug delivery and miRNA targeting. The MSNPs are easily synthesized and loaded with the anti‐cancer drug temozolomide (TMZ), and the particle surface is decorated with a polyarginine‐peptide nucleic acid conjugate (R8‐PNA) targeting miR221. The synergistic effect of TMZ and R8‐PNA has a dramatic impact on the human T98G tumor cell line.