Nanoparticle-Delivered Antisense MicroRNA-21 Enhances the Effects of Temozolomide on Glioblastoma Cells
Nanoparticle-Delivered Antisense MicroRNA-21 Enhances the Effects of Temozolomide on Glioblastoma Cells
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DOI：
10.1021/acs.molpharmaceut.5b00694
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发表时间：
2015-12-01
影响因子：
4.9
通讯作者：
Massoud, Tank F.
中科院分区：
文献类型：
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作者：
Ananta, Jeyarama S.;Paulmurugan, Ramasamy;Massoud, Tank F.
胶质母细胞瘤（GBM）通常对其标准药物治疗替莫唑胺（TMZ）表现出高IC 50值。microRNA-21（miR-21）是在GBM中过表达的oncomiR，因此控制胶质瘤生物学的重要方面。我们假设，PLGA纳米颗粒携带反义miR-21的胶质母细胞瘤细胞可能有利于敲低内源性miR-21 TMZ治疗前。包封反义miR-21的PLGA纳米颗粒在U87 MG、LN 229和T98 G细胞中的miR-21功能的细胞内递送和持续沉默（p < 0.01）中是有效的。在U87 MG细胞中，在TMZ处理后，先前的反义miR-21递送显著减少了活细胞的数量（p < 0.001），并增加了（1.6倍）G2/M期的细胞周期停滞。共处理后，miR-21靶基因PTEN（67%）和caspase-3（15%）过表达。这种有前途的基于PLGA纳米颗粒的平台用于将反义miR-21递送至GBM是细胞培养中的有效共治疗策略，在未来临床转化之前无需进一步研究。
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.