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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