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

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Mariarosa Mazza
  • Hassan Ahmad
  • Giulia Agliardi
  • Andrew T King

Abstract

Aim: To develop a nonviral 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 nonphagocytic (U-87 MG) cells via endocytosis and passive translocation. siPLK1 delivered using PNFs reduced the expression of polo-like kinase 1 mRNA and induced cell death in a panel of immortalized and glioblastoma-derived stem cells. Moreover, targeting MMP2 using 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 with the untreated tumor bearing animals. Conclusion: Our results suggest that this nanomedicine-based RNA interference approach deserves further investigation as a potential brain tumor therapeutic tool.

Bibliographical metadata

Original languageEnglish
Pages (from-to)3127-3142
Number of pages16
Journalnanomedicine
Volume14
Issue number24
Early online date19 Dec 2019
DOIs
Publication statusPublished - Dec 2019