Targeted delivery of tumor suppressor microRNA-1 by transferrin-conjugated lipopolyplex nanoparticles to patient-derived glioblastoma stem cells

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

Research output: Contribution to journalArticle

46 Scopus citations

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.

Original languageEnglish (US)
Article numberA09
Pages (from-to)839-846
Number of pages8
JournalCurrent Pharmaceutical Biotechnology
Volume15
Issue number9
StatePublished - Jan 1 2015

    Fingerprint

Keywords

  • Cancer initiating cells
  • Cancer stem cells
  • Glioma stem cells
  • Targeted delivery
  • Transferrin-conjugated nanoparticles

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

Cite this

Wang, X., Huang, X., Yang, Z., Gallego-Perez, D., Ma, J., Zhao, X., Xie, J., Nakano, I., & James Lee, L. (2015). Targeted delivery of tumor suppressor microRNA-1 by transferrin-conjugated lipopolyplex nanoparticles to patient-derived glioblastoma stem cells. Current Pharmaceutical Biotechnology, 15(9), 839-846. [A09].