Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2/Bax in human neuroblastoma
Nanoparticle delivery of curcumin induces cellular hypoxia and ROS-mediated apoptosis via modulation of Bcl-2/Bax in human neuroblastoma
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DOI：
10.1039/c7nr02770b
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发表时间：
2017-08-07
期刊：
影响因子：
6.7
通讯作者：
Seal, Sudipta
中科院分区：
文献类型：
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作者：
Kalashnikova, Irina;Mazar, Joseph;Seal, Sudipta
在这项研究中，合成了几种具有抗癌特性的纳米氧化钙和含有姜黄素的葡聚糖纳米氧化钙，并将其用于治疗儿童神经母细胞瘤。在MYCN扩增和非扩增细胞系的神经母细胞瘤模型中，研究了这些制剂的抗癌活性。研究发现，包被葡聚糖并负载姜黄素的CeO_2纳米粒子可诱导神经母细胞瘤细胞大量死亡(MYCN上调和正常表达的细胞系的细胞活力分别下降2倍和1.6倍；(STAR)p<；0.05)，而对健康细胞没有或仅产生轻微的毒性(100µM；(STAR)p<；0.01没有毒性)。该配方可引起长期的氧化应激，稳定HIF-1α，并诱导依赖于caspase的细胞凋亡(比对照增加2.4倍；(STAR)p<；0.05)。总体而言，纳米治疗在MYCN扩增的细胞中显示出更明显的效果，这些细胞传统上对药物治疗更具抵抗力。这些结果代表了一种非常有希望的替代小分子药物疗法治疗强健癌症的方法。
In this study, several formulations of nanoceria and dextran-nanoceria with curcumin, each demonstrated to have anti-cancer properties, were synthesized and applied as treatment for human childhood neuroblastoma. The anti-cancer activities of these formulations were explored in neuroblastoma models of both MYCN-amplified and non-amplified cell lines. Ceria nanoparticles, coated with dextran and loaded with curcumin, were found to induce substantial cell death in neuroblastoma cells (up to a 2-fold and a 1.6-fold decrease in cell viability for MYCN-upregulated and normal expressing cell lines, respectively; (star)p < 0.05) while producing no or only minor toxicity in healthy cells (no toxicity at 100 mu M; (star star)p < 0.01). This formulation evokes prolonged oxidative stress, stabilizing HIF-1 alpha, and inducing caspase-dependent apoptosis (up to a 2.4-fold increase over control; (star)p < 0.05). Overall, nano-therapeutic treatments showed a more pronounced effect in MYCN-amplified cells, which are traditionally more resistant to drug therapies. These results represent a very promising alternative to small molecule drug therapies for robust cancers.