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.

中文翻译：

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具有超顺磁性氧化铁纳米粒子的MXD3反义寡核苷酸：一种针对神经母细胞瘤的新靶向方法。

神经母细胞瘤（NB）是儿童中最常见的颅外实体瘤。积极形式的NB的结果仍然很差。这项研究的目的是使用反义寡核苷酸（ASO）和超顺磁性氧化铁（SPIO）纳米粒子（NPs）作为传递载体，开发一种针对NB的新型分子靶向疗法，其靶向转录调节剂MAX二聚化蛋白3（MXD3） ）。先前我们发现MXD3在高危NB中高表达，起抗凋亡因子的作用。因此，它可以成为良好的治疗靶标。在这项研究中，我们开发了两种ASO-NP配合物，它们通过静电共轭与聚乙烯亚胺涂层的SPIO NPs进行化学共轭，并通过化学共轭与在胺官能化的SPIO NPs上的两亲聚合物进行共轭。两种ASO-NP复合物均显示MXD3敲低，导致NB细胞凋亡。