Articles | 2019

Nanomedicine, 2019, in press

Hampering brain tumor proliferation and migration using peptide nanofiber:siPLK1/MMP2 complexes

Mariarosa Mazza, Hassan Ahmad, Marilena Hadjidemetriou, Giulia Agliardi, Omar N. Pathmanaban, Andrew T. King, Brian W. Bigger, Sandra Vranic*, Kostas Kostarelos*

Aim: To develop a non-viral tool for the delivery of siRNA to brain tumor cells using peptide nanofibers (PNFs). Materials & methods: Uptake of PNFs was evaluated by confocal microscopy and flow cytometry. Gene silencing was determined by RT-qPCR and cell invasion assay. Results: PNFs enter phagocytic (BV-2) and non-phagocytic (U-87 MG) cells via endocytosis and passive translocation. siPLK1 delivered using PNFs reduced the expression of PLK1 mRNA and induced cell death in a panel of immortalized and glioblastoma-derived stem cells. Moreover, PNF:siMMP2 reduced the invasion capacity of U-87 MG cells. We show that stereotactic intra-tumoral administration of PNF:siPLK1 significantly extends the survival of tumor bearing mice comparing to the untreated tumor bearing animals. Conclusions: Our results suggest that this nanomedicine-based RNAi approach deserves further investigation as a potential brain tumor therapeutic tool.