A novel peptide for microRNA delivery to medulloblastoma cells

Abstract

Medulloblastoma is a paediatric brain cancer categorised into various subtypes that have differing prognostic outcomes
for patients. As with other cancers, microRNAs have been implicated in medulloblastoma pathogenesis and
the loss of specific miRNAs appears to contribute to the disease. There is therefore an urgent need to develop
miRNA-replacement therapies for medulloblastoma. However, methods for targeted delivery of small RNAs to medulloblastoma
cells have not been fully established. As a step towards tackling this challenge, we have developed
self-assembling peptide nanoparticles for small RNA delivery to medulloblastoma cells. We generated an amphiphilic
peptide, TY-28, using solid-phase peptide synthesis and combined TY-28 with miR-124-3p. Analysis of the resulting
complexes by electron microscopy and dynamic light scattering confirmed the formation of nanoparticles. The ability
of the NPs to penetrate cells was monitored by labelling the miRNA with a fluorescent dye. The NP:miRNA complexes
were readily internalised by group 3 medulloblastoma cells, and the accumulation of the complexes increased over
time. Levels of uptake were 6-fold higher at 24 hours compared to 4 hours in serum-free medium. The uptake of the
NPs complexes by the cells did not differ in the presence and absence of serum, suggesting the presence of serum
did not affect complex stability. Our findings point to the translational potential of self-assembled NPs to delivery miRNA
mimics to medulloblastoma cells.