Journal
NANOMEDICINE
Volume 14, Issue 24, Pages 3127-3142Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2019-0298
Keywords
drug delivery; gene therapy; glioblastoma; nanomedicine; peptide nanofibers; siRNA; U-87 MG
Funding
- University of Manchester
- 'RADDEL' Marie Curie Initial Training Network (ITN) grant under the EU's FP7 PEOPLE program
- EPSRC [EP/K005014/1] Funding Source: UKRI
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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.
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