Erlotinib-Conjugated Iron Oxide Nanoparticles as a Smart Cancer-Targeted Theranostic Probe for MRI.
Erlotinib-Conjugated Iron Oxide Nanoparticles as a Smart Cancer-Targeted Theranostic Probe for MRI.
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DOI：
10.1038/srep36650
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发表时间：
2016-11-11
影响因子：
4.6
通讯作者：
Huang HS
中科院分区：
文献类型：
--
作者：
Ali AA;Hsu FT;Hsieh CL;Shiau CY;Chiang CH;Wei ZH;Chen CY;Huang HS
我们设计并合成了新型的治疗诊断纳米颗粒，这些纳米颗粒在靶向治疗和通过MRI对肿瘤进行非侵入性实时监测方面显示出相当大的临床应用潜力。我们的纳米颗粒是超小的，具有超顺磁性氧化铁核，与厄洛替尼缀合（FeDC-E NPs）。这种智能靶向纳米颗粒优先在细胞内释放药物，而不是进入血流，并特异性识别和杀死过表达EGFR的癌细胞，同时对EGFR阴性细胞无毒。MRI、透射电子显微镜和普鲁士蓝染色结果表明，在EGFR过表达细胞中，FeDC-E纳米颗粒的细胞摄取和细胞内蓄积显著高于非厄洛替尼缀合的纳米颗粒。FeDC-E NPs可抑制EGFR-ERK-NF-κB信号通路，从而抑制高度侵袭性和迁移性CL 1 -5-F4癌细胞的迁移和侵袭能力。BALB/c裸鼠体内移植瘤实验表明，FeDC-E纳米粒能有效抑制肿瘤生长。与非靶向对照氧化铁纳米颗粒相比，小鼠的T2加权MRI图像显示用FeDC-E纳米颗粒治疗后肿瘤内的标准化信号显著降低。这是第一项使用厄洛替尼作为纳米颗粒小分子靶向剂的研究。
We designed and synthesized novel theranostic nanoparticles that showed the considerable potential for clinical use in targeted therapy, and non-invasive real-time monitoring of tumors by MRI. Our nanoparticles were ultra-small with superparamagnetic iron oxide cores, conjugated to erlotinib (FeDC-E NPs). Such smart targeted nanoparticles have the preference to release the drug intracellularly rather than into the bloodstream, and specifically recognize and kill cancer cells that overexpress EGFR while being non-toxic to EGFR-negative cells. MRI, transmission electron microscopy and Prussian blue staining results indicated that cellular uptake and intracellular accumulation of FeDC-E NPs in the EGFR overexpressing cells was significantly higher than those of the non-erlotinib-conjugated nanoparticles. FeDC-E NPs inhibited the EGFR–ERK–NF-κB signaling pathways, and subsequently suppressed the migration and invasion capabilities of the highly invasive and migrative CL1-5-F4 cancer cells. In vivo tumor xenograft experiments using BALB/c nude mice showed that FeDC-E NPs could effectively inhibit the growth of tumors. T2-weighted MRI images of the mice showed significant decrease in the normalized signal within the tumor post-treatment with FeDC-E NPs compared to the non-targeted control iron oxide nanoparticles. This is the first study to use erlotinib as a small-molecule targeting agent for nanoparticles.
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N-钙粘着蛋白在乳腺癌细胞中的外源表达会诱导细胞迁移，侵袭和转移。
影响因子：
7.8
作者：
Hazan, R B;Phillips, G R;Qiao, R F;Norton, L;Aaronson, S A
通讯作者：
Aaronson, S A
影响因子：
3.7
作者：
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通讯作者：
Huang HS
影响因子：
8
作者：
Bhat-Nakshatri, P;Sweeney, CJ;Nakshatri, H
通讯作者：
Nakshatri, H
DOI：
10.1073/pnas.1107385108
发表时间：
2011-07-12
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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Pourgholami, Mohammad H.