In vitro and in vivo targeting of hollow gold nanoshells directed at epidermal growth factor receptor for photothermal ablation therapy
In vitro and in vivo targeting of hollow gold nanoshells directed at epidermal growth factor receptor for photothermal ablation therapy
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DOI：
10.1158/1535-7163.mct-08-0016
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发表时间：
2008-06-01
影响因子：
5.7
通讯作者：
Li, Chun
中科院分区：
文献类型：
--
作者：
Melancon, Marites P.;Lu, Wei;Li, Chun
激光诱导光疗是一种新型的电磁辐射治疗癌症的方法。靶向等离子体金纳米粒子的使用可以减少选择性肿瘤细胞破坏所需的激光能量。然而，目前使用的金纳米颗粒靶向递送到肿瘤细胞的能力是有限的。在这里，我们描述了一类新的分子特异性光热耦合剂的基础上的中空金纳米壳（HAuNS;平均直径，类似于30 nm）共价连接到单克隆抗体针对表皮生长因子受体（EGFR）。所得的抗EGFR-HAuNS在近红外区域表现出优异的胶体稳定性和有效的光热效应。通过对来自纳米壳的散射光进行成像，在体外显示了EGFR-阳性A431肿瘤细胞中EGFR介导的抗EGFR-HAuNS的选择性摄取，而不是IgG-HAuNS对照。用近红外激光照射用抗EGFR-HAuNS处理的A431细胞导致这些细胞的选择性破坏。相比之下，用单独的抗EGFR-HAuNS、单独的激光或IgG-HAuNS加激光处理的细胞没有显示出对细胞活力的可观察到的影响。使用In-111标记的HAuNS，我们表明抗EGFR-HAuNS可以以6.8%ID/g递送至EGFR阳性肿瘤，并且具有来自纳米壳的散射信号的切除肿瘤的显微图像证实了与IgG-HAuNS相比，抗EGFR-HAuNS优先递送至A431肿瘤。不存在二氧化硅核、相对小的粒径和高肿瘤摄取以及不存在稳定其他金纳米颗粒所需的细胞毒性表面活性剂表明免疫HAuNS具有扩展到体内分子治疗的潜力。
Laser-induced phototherapy is a new therapeutic use of electromagnetic radiation for cancer treatment. The use of targeted plasmonic gold nanoparticles can reduce the laser energy necessary for selective tumor cell destruction. However, the ability for targeted delivery of the currently used gold nanoparticles to tumor cells is limited. Here, we describe a new class of molecular specific photothermal coupling agents based on hollow gold nanoshells (HAuNS; average diameter, similar to 30 nm) covalently attached to monoclonal antibody directed at epidermal growth factor receptor (EGFR). The resulting anti-EGFR-HAuNS exhibited excellent colloidal stability and efficient photothermal effect in the near-infrared region. EGFR-mediated selective uptake of anti-EGFR-HAuNS in EGFR-positive A431 tumor cells but not IgG-HAuNS control was shown in vitro by imaging scattered light from the nanoshells. Irradiation of A431 cells treated with anti-EGFR-HAuNS with near-infrared laser resulted in selective destruction of these cells. In contrast, cells treated with anti-EGFR-HAuNS alone, laser alone, or IgG-HAuNS plus laser did not show observable effect on cell viability. Using In-111-labeled HAuNS, we showed that anti-EGFR-HAuNS could be delivered to EGFR-positive tumors at 6.8% ID/g, and the microscopic image of excised tumor with scattering signal from nanoshells confirmed preferential delivery to A431 tumor of anti-EGFR-HAuNS compared with IgG-HAuNS. The absence of silica core, the relatively small particle size and high tumor uptake, and the absence of cytotoxic surfactant required to stabilize other gold nanoparticles suggest that immuno-HAuNS have the potential to extend to in vivo molecular therapy.