Effectiveness of porous silicon nanoparticle treatment at inhibiting the migration of a heterogeneous glioma cell population

Youssef Abdalla,Wing Yin Tong,Nicolas H Voelcker,Ermei Mäkilä,Meihua Luo,Bryan W Day

doi:10.1186/s12951-021-00798-4

Abstract

BackgroundApproximately 80% of brain tumours are gliomas. Despite treatment, patient mortality remains high due to local metastasis and relapse. It has been shown that transferrin-functionalised porous silicon nanoparticles (Tf@pSiNPs) can inhibit the migration of U87 glioma cells. However, the underlying mechanisms and the effect of glioma cell heterogeneity, which is a hallmark of the disease, on the efficacy of Tf@pSiNPs remains to be addressed.ResultsHere, we observed that Tf@pSiNPs inhibited heterogeneous patient-derived glioma cells’ (WK1) migration across small perforations (3 μm) by approximately 30%. A phenotypical characterisation of the migrated subpopulations revealed that the majority of them were nestin and fibroblast growth factor receptor 1 positive, an indication of their cancer stem cell origin. The treatment did not inhibit cell migration across large perforations (8 μm), nor cytoskeleton formation. This is in agreement with our previous observations that cellular-volume regulation is a mediator of Tf@pSiNPs’ cell migration inhibition. Since aquaporin 9 (AQP9) is closely linked to cellular-volume regulation, and is highly expressed in glioma, the effect of AQP9 expression on WK1 migration was investigated. We showed that WK1 migration is correlated to the differential expression patterns of AQP9. However, AQP9-silencing did not affect WK1 cell migration across perforations, nor the efficacy of cell migration inhibition mediated by Tf@pSiNPs, suggesting that AQP9 is not a mediator of the inhibition.ConclusionThis in vitro investigation highlights the unique therapeutic potentials of Tf@pSiNPs against glioma cell migration and indicates further optimisations that are required to maximise its therapeutic efficacies.Graphic

Highlights

We previously demonstrated that transferrin-functionalised porous silicon nanoparticles (Tf@Porous silicon nanoparticles (pSiNPs)) inhibit glioma cell migration by approximately 40% using the immortalised U87 glioma cell line model [10]
We found that WK1 cells treated with Tf@pSiNPs were able to migrate across 8 μm transwell inserts, and no significant difference in cell migration index (CMI) was observed, compared to control cells (Fig. 4b)
We observed that Tf@pSiNPs significantly inhibited WK1 cell migration through the interruption of cellular-volume regulation

Summary

Introduction

It has been shown that transferrin-functionalised porous silicon nanoparticles (Tf@pSiNPs) can inhibit the migration of U87 glioma cells. 80% of brain tumours are gliomas, primary tumours that arise from neuroglial stem or progenitor cells [1]. It is clinically evident that despite 99% resection of the glioma mass, relapse occurs within 6 months [9]. This is partly due to the migrated cells left behind after incomplete resection readopting a proliferation phenotype and reforming a tumour mass [5]. The absence of measures to inhibit glioma cell migration presents a major barrier to realise a complete treatment of GBM [5]

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