Nanoparticle-Delivered Antisense MicroRNA-21 Enhances
the Effects of Temozolomide on Glioblastoma Cells
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Abstract
Glioblastoma
(GBM) generally exhibits high IC<sub>50</sub> 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 (<i>p</i> < 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 (<i>p</i> < 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 <i>PTEN</i> (by 67%) and <i>caspase-3</i> (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