Development of red blood cell-derived extracellular particles as a biocompatible nanocarrier of microRNA-204 (REP-204) to harness anti-neuroblastoma effect.
Wararat ChiangjongJirawan PanachanSujitra KeadsantiDavid S NewburgArdythe L MorrowSuradej HongengSomchai ChutipongtanatePublished in: Nanomedicine : nanotechnology, biology, and medicine (2024)
Neuroblastoma (NB) is the most common extracranial solid tumor in the pediatric population with a high degree of heterogeneity in clinical outcomes. Upregulation of the tumor suppressor miR-204 in neuroblastoma is associated with good prognosis. Although miR-204 has been recognized as a potential therapeutic candidate, its delivery is unavailable. We hypothesized that REP-204, the red blood cell-derived extracellular particles (REP) with miR-204 loading, can suppress neuroblastoma cells in vitro. After miR-204 loading by electroporation, REP-204, but not REP carriers, inhibited the viability, migration, and 3D spheroid growth of neuroblastoma cells regardless of MYCN amplification status. SWATH-proteomics revealed that REP-204 treatment may trigger a negative regulation of mRNA splicing by the spliceosome, suppression of amino acid metabolism and protein production, and prevent SLIT/ROBO signaling-mediated cell migration, to halt neuroblastoma tumor growth and metastasis. The therapeutic efficacy of REP-204 should be further investigated in preclinical models and clinical studies.
Keyphrases
- cell proliferation
- long non coding rna
- long noncoding rna
- induced apoptosis
- cell migration
- red blood cell
- amino acid
- cell cycle arrest
- poor prognosis
- single cell
- drug delivery
- stem cells
- mass spectrometry
- cell death
- high resolution
- mesenchymal stem cells
- ionic liquid
- bone marrow
- cell therapy
- combination therapy
- nucleic acid
- smoking cessation