TY  - JOUR
N2  - Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.
ID  - discovery10146556
UR  - https://doi.org/10.1038/s41598-020-59146-5
PB  - Springer Science and Business Media LLC
SN  - 2045-2322
JF  - Scientific Reports
A1  - Sheykhzadeh, Sana
A1  - Luo, Meihua
A1  - Peng, Bo
A1  - White, Jacinta
A1  - Abdalla, Youssef
A1  - Tang, Tweety
A1  - Mäkilä, Ermei
A1  - Voelcker, Nicolas H
A1  - Tong, Wing Yin
KW  - Apoptosis
KW  -  Brain Neoplasms
KW  -  Cell Movement
KW  -  Cell Proliferation
KW  -  Drug Delivery Systems
KW  -  Extracellular Space
KW  -  Glioblastoma
KW  -  Humans
KW  -  Nanoparticles
KW  -  Porosity
KW  -  Silicon
KW  -  Transferrin
KW  -  Tumor Cells
KW  -  Cultured
TI  - Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space
AV  - public
Y1  - 2020/02/11/
VL  - 10
IS  - 1
N1  - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
ER  -