A novel peptide for microRNA delivery to medulloblastoma cells

Abstract

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