Sheykhzadeh, Sana;
Luo, Meihua;
Peng, Bo;
White, Jacinta;
Abdalla, Youssef;
Tang, Tweety;
Mäkilä, Ermei;
... Tong, Wing Yin; + view all
(2020)
Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space.
Scientific Reports
, 10
(1)
, Article 2320. 10.1038/s41598-020-59146-5.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-020-59146-5 |
| Publisher version: | https://doi.org/10.1038/s41598-020-59146-5 |
| Language: | English |
| Additional information: | 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. |
| Keywords: | Apoptosis, Brain Neoplasms, Cell Movement, Cell Proliferation, Drug Delivery Systems, Extracellular Space, Glioblastoma, Humans, Nanoparticles, Porosity, Silicon, Transferrin, Tumor Cells, Cultured |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10146556 |
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