An MRI-visible non-viral vector for targeted Bcl-2 siRNA delivery to neuroblastoma.
An MRI-visible non-viral vector for targeted Bcl-2 siRNA delivery to neuroblastoma.
复制标题
一种 MRI 可见的非病毒载体，用于将 Bcl-2 siRNA 靶向递送至神经母细胞瘤。
DOI：
10.2147/ijn.s32900
复制
发表时间：
2012
影响因子：
8
通讯作者：
Shuai X
中科院分区：
文献类型：
--
作者：
Shen M;Gong F;Pang P;Zhu K;Meng X;Wu C;Wang J;Shan H;Shuai X
合成了聚乙二醇接枝聚乙烯亚胺（PEG-g-PEI），并将其与神经母细胞瘤细胞特异性配体GD 2单链抗体（scAbGD 2）功能化，以有效地将Bcl-2 siRNA导入神经母细胞瘤细胞。该聚合物首先与超顺磁性氧化铁纳米颗粒（SPION）复合以获得MRI可见的靶向非病毒载体（scAbGD 2-PEG-g-PEI-SPION），然后与Bcl-2 siRNA复合以形成显示低细胞毒性的纳米颗粒。通过磁共振成像成功地在体内和体外验证了scAbGD 2-PEG-g-PEI-SPION的靶向能力。在人神经母细胞瘤细胞系SK-N-SH中，靶向单链抗体编码的多聚物比非靶向单链抗体更有效地转移Bcl-2siRNA，导致Bcl-2 mRNA表达抑制46.34%。因此，scAbGD 2-PEG-g-PEI-SPION实现了高达50.76%的细胞凋亡水平和显著的肿瘤生长抑制，这表明scAbGD 2-PEG-g-PEI-SPION是一种有希望的磁共振成像可见的非病毒载体，用于靶向神经母细胞瘤siRNA治疗和诊断。
Polyethylene glycol-grafted polyethylenimine (PEG-g-PEI) which was functionalized with a neuroblastoma cell-specific ligand, the GD2 single chain antibody (scAbGD2), was synthesized in order to effectively deliver Bcl-2 siRNA into neuroblastoma cells. This polymer was complexed first with superparamagnetic iron oxide nanoparticle (SPION) to get a MRI-visible targeted non-viral vector (scAbGD2-PEG-g-PEI-SPION) and then with Bcl-2 siRNA to form nanoparticles showing low cytotoxicity. The targeting capacity of scAbGD2-PEG-g-PEI-SPION was successfully verified in vivo and in vitro by magnetic resonance imaging. The single chain antibody encoded targeted polyplex was more effective in transferring Bcl-2 siRNA than the nontargeting one in SK-N-SH cells, a human neuroblastoma cell line, resulting in a 46.34% inhibition in the expression of Bcl-2 mRNA. Consequently, a high level of cell apoptosis up to 50.76% and a significant suppression of tumor growth were achieved, which indicates that scAbGD2-PEG-g-PEI-SPION is a promising magnetic resonance imaging-visible non-viral vector for targeted neuroblastoma siRNA therapy and diagnosis.