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: Jeyarama S Ananta, Ramasamy Paulmurugan, Tarik F Massoud
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 12 Issue 12 Pg. 4509-17 (Dec 07 2015) ISSN: 1543-8392 [Electronic] United States
• PMID: 26559642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Antisense Elements (Genetics)
• MIRN21 microRNA, human
• MicroRNAs
• Dacarbazine
• PTEN Phosphohydrolase
• PTEN protein, human
• Caspase 3
• Temozolomide

Topics

• Antineoplastic Agents, Alkylating (pharmacology)
• Antisense Elements (Genetics) (genetics)
• Brain Neoplasms (drug therapy, genetics)
• Caspase 3 (genetics)
• Cell Line, Tumor
• Dacarbazine (analogs & derivatives, pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioblastoma (drug therapy, genetics)
• Glioma (drug therapy, genetics)
• Humans
• MicroRNAs (genetics)
• Nanoparticles (administration & dosage)
• PTEN Phosphohydrolase (genetics)
• Temozolomide