Targeted Delivery of Tumor Suppressor microRNA-1 by Transferrin- Conjugated Lipopolyplex Nanoparticles to Patient-Derived Glioblastoma Stem Cells

Author(s): Xinmei Wang, Xiaomeng Huang, Zhaogang Yang, Daniel Gallego-Perez, Junyu Ma, Xi Zhao, Jing Xie, Ichiro Nakano, L. James Lee.

Journal Name: Current Pharmaceutical Biotechnology

Volume 15 , Issue 9 , 2014

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Abstract:

Objective: Among heterogeneous glioblastoma multiforme (GBM) cells, glioblastoma stem cells (GSCs) is a subpopulation having a critical role in tumor initiation and therapy resistance. Thus targeting GSCs would be an essential step to completely eradicate this lethal disease. MicroRNA-1 (miR-1) expression is deregulated in GBM patients and restoration of miR-1 by viral-vector in GBM cells has been demonstrated to inhibit tumor initiation and attenuate cell migration. Here, we show that a transferrin-targeting non-invasive nanoparticle delivery system (Tf-NP) can efficiently deliver miR-1 to GBM patient-derived GSC-enriched sphere cultures (GBM spheres). Methods: Delivery efficiency of the transferrin- targeting non-invasive nanoparticle was investigated by flow cytometry and further confirmed by confocal microscopy. The levels of miR-1 and its target molecules in GBM spheres were measured by qRT-PCR and immunoblotting. Migration capacity of Tf-NP-miR-1 treated GBM spheres were evaluated by transwell migration assay. Results: Tf-NPmiR- 1 treatment resulted in an over 200-fold increase of mature miR-1 compared to free miR-1 and Tf-NP-miR negative control (Tf-NP-miR-NC). Transferrin-mediated NP delivery resulted in a 3-fold higher delivery efficiency compared to NP without transferrin modification. Tf-NP-miR-1 treatment on GBM spheres significantly inhibited migration of GBM spheres by 30–50% with associated decline of MET and EGFR expression. Our data supported that Tf-NP could be used as an efficient and effective delivery system which has high potential to benefit the development of miR-based therapeutics for GBM treatment.

Keywords: Cancer initiating cells, cancer stem cells, glioma stem cells, targeted delivery, transferrin-conjugated nanoparticles.

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Article Details

VOLUME: 15
ISSUE: 9
Year: 2014
Page: [839 - 846]
Pages: 8
DOI: 10.2174/1389201015666141031105234
Price: $58

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