Formulation of magnetic nanocomposites for intracellular delivery of micro-RNA for MYCN inhibition in neuroblastoma

Abstract

Neuroblastoma, which accounts for almost 6% of all cancers in infants, originates from the sympathoadrenal progenitor cells within the neural crest. Approximately 25 % of neuroblastoma cases result from the amplification of the MYC-related oncogene MYCN, thus leading to high disease risk and poor prognosis; hence, studies focusing on the inhibition of MYCN are indispensable. Interestingly, microRNA-34 (miR-34) is a prospective candidate for cancer therapy because of its oncogenic and tumor-suppressing ability. This study presents the synthesis, characterization, and application of cationic magnetic nanocomposites (MNCs) comprising branched polyethylenimine (PEI)-coated iron oxide nanoparticles (IONPs). These positively charged MNCs possess the ability to penetrate the negatively charged cell wall for the delivery of miR-34a molecules into cancerous cells. The characteristic peaks at 3380, 1620, 2900, and 2840 cm−1 corresponding to −NH− and −CH2− groups suggest successful coating of PEI on the surface of IONPs. The X-ray powder diffraction (XRPD) peak of the prepared MNCs at 2θ = 35.44° resembled that of magnetite (Fe3O4, (311)). The transfection efficiency was enhanced through a magnetic field that enabled a very rapid concentration of the completely delivered vector dose onto cells. Additionally, the results of small-angle neutron scattering (SANS) revealed that core heat was generated and subsequently led to shell softening, which was activated by an alternative magnetic field (AMF). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that MNCs did not exhibit any significant toxicity against the tested cells. The increased amplification of miR-34a led to the suppression of the MYCN protein, which consequently inhibited the growth of neuroblastoma cells.