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

Journal of Nanobiotechnology

Meihua Luo¹  Nicolas H. Voelcker²  Wing Yin Tong³  Ermei Mäkilä⁴  Youssef Abdalla⁵  Bryan W. Day⁶ 

[1] Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutics Science, Monash University, Parkville Campus, 381 Royal Parade, 3052, Parkville, VIC, Australia;Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong;Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutics Science, Monash University, Parkville Campus, 381 Royal Parade, 3052, Parkville, VIC, Australia;Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong;Commonwealth Scientific and Industrial Research Organization (CSIRO), Clayton, VIC, Australia;Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, VIC, Australia;Department of Materials Science and Engineering, Monash University, Clayton, VIC, Australia;Leibniz Institut für Neue Materialien (INM), Campus D2 2, 66123, Saarbrücken, Germany;Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutics Science, Monash University, Parkville Campus, 381 Royal Parade, 3052, Parkville, VIC, Australia;Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, VIC, Australia;Industrial Physics Laboratory, Department of Physics and Astronomy, University of Turku, Turku, Finland;School of Pharmacy, University College London, 29-39 Brunswick Square, WC1N 1AX, London, UK;Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutics Science, Monash University, Parkville Campus, 381 Royal Parade, 3052, Parkville, VIC, Australia;Sid Faithfull Brain Cancer Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia;

关键词: Transferrin;    Silicon nanoparticles;    Glioma;    Glioblastoma;    Cell migration;    aquaporin 9;    Cancer stem cells;   

DOI  :  10.1186/s12951-021-00798-4

来源: Springer

【 摘 要 】

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 Abstract

【 授权许可】

CC BY