MXD3 antisense oligonucleotide with superparamagnetic iron oxide nanoparticles: A new targeted approach for neuroblastoma

Sakiko Yoshida, Connie Duong, Michael Oestergaard, Michael Fazio, Cathy Chen, Rachael Peralta, Shuling Guo, Punit P. Seth, Yueju Li, Laurel Beckett, Nitin Nitin, Noriko Satake

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Neuroblastoma (NB) is the most common extracranial solid tumor in children. The outcomes for aggressive forms of NB remain poor. The aim of this study was to develop a new molecular-targeted therapy for NB using an antisense oligonucleotide (ASO) and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), as a delivery vehicle, targeting the transcription regulator MAX dimerization protein 3 (MXD3). We previously discovered that MXD3 was highly expressed in high-risk NB, acting as an anti-apoptotic factor; therefore, it can be a good therapeutic target. In this study, we developed two ASO-NP complexes using electrostatic conjugation to polyethylenimine-coated SPIO NPs and chemical conjugation to amphiphilic polymers on amine-functionalized SPIO NPs. Both ASO-NP complexes demonstrated MXD3 knockdown, which resulted in apoptosis in NB cells. ASO chemically-conjugated NP complexes have the potential to be used in the clinic as they showed great efficacy with minimum NP-associated cytotoxicity.

Original languageEnglish (US)
Article number102127
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume24
DOIs
StatePublished - Feb 2020

Keywords

  • Antisense oligonucleotide
  • Gene silencing
  • Nanoparticle
  • Neuroblastoma
  • Targeted therapy

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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