Anti-miR delivery strategies to bypass the blood-brain barrier in glioblastoma therapy

Dong Geon Kim, Kang Ho Kim, Yun Jee Seo, Heekyoung Yang, Eric G. Marcusson, Eunju Son, Kyoungmin Lee, Jason K. Sa, Hye Won Lee, Do Hyun Nam

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Small non-coding RNAs called miRNAs are key regulators in various biological processes, including tumor initiation, propagation, and metastasis in glioblastoma as well as other cancers. Recent studies have shown the potential for oncogenic miRNAs as therapeutic targets in glioblastoma. However, the application of antisense oligomers, or anti-miRs, to the brain is limited due to the blood-brain barrier (BBB), when administered in the traditional systemic manner. To induce a therapeutic effect in glioblastoma, anti-miR therapy requires a robust and effective delivery system to overcome this obstacle. To bypass the BBB, different delivery administration methods for anti-miRs were evaluated. Stereotaxic surgery was performed to administer anti- Let-7 through intratumoral (ITu), intrathecal (ITh), and intraventricular (ICV) routes, and each method's efficacy was determined by changes in the expression of anti- Let-7 target genes as well as by immunohistochemical analysis. ITu administration of anti-miRs led to a high rate of anti-miR delivery to tumors in the brain by both bolus and continuous administration. In addition, ICV administration, compared with ITu administration, showed a greater distribution of the miR across entire brain tissues. This study suggests that local administration methods are a promising strategy for anti-miR treatment and may overcome current limitations in the treatment of glioblastoma in preclinical animal models.

Original languageEnglish
Pages (from-to)29400-29411
Number of pages12
JournalOncotarget
Volume7
Issue number20
DOIs
Publication statusPublished - 2016 May 17
Externally publishedYes

Keywords

  • Anti-miR
  • Delivery efficiency
  • Glioblastoma
  • Intratumoral injection
  • Intraventricular injection

ASJC Scopus subject areas

  • Oncology

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