Controlled release of PEG chain from gold nanorods: Targeted delivery to tumor
Controlled release of PEG chain from gold nanorods: Targeted delivery to tumor
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DOI：
10.1016/j.bmc.2010.04.070
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发表时间：
2010-06-15
影响因子：
3.5
通讯作者：
Katayama, Yoshiki
中科院分区：
文献类型：
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作者：
Niidome, Takuro;Ohga, Akira;Katayama, Yoshiki
金纳米棒在近红外区域表现出强烈的光吸收，其深入组织。由于吸收的光能被转化为热量，金纳米棒有望作为体内生物成像的造影剂和光热治疗的热转换器。为了构建用于肿瘤的金纳米棒靶向递送系统，将在恶性肿瘤上特异性表达的尿激酶型纤溶酶原激活物（uPA）的肽底物插入PEG链和金纳米棒表面之间。换句话说，我们构建了PEG-肽修饰的金纳米棒。将金纳米棒与uPA混合后，PEG链从金表面释放，随后发生纳米棒聚集。聚集体的形成以900 nm处光吸收的降低来监测。肿瘤匀浆诱导这种吸收显著减少。与对照金纳米棒相比，PEG肽修饰的金纳米棒在体外与表达uPA的细胞结合的量更大，对照金纳米棒具有混乱的肽序列。PEG-肽修饰的金纳米棒静脉注射给荷瘤小鼠后，其在肿瘤中的蓄积量明显高于对照组，但肽在金纳米棒表面的浓度是影响其生物分布的关键因素。这种对uPA活性有响应的靶向递送系统有望成为肿瘤生物成像和光热肿瘤治疗的有力工具。(C)2010爱思唯尔有限公司版权所有。
Gold nanorods exhibit strong absorbance of light in the near infrared region, which penetrates deeply into tissues. Since the absorbed light energy is converted into heat, gold nanorods are expected to act as a contrast agent for in vivo bioimaging and as a thermal converter for photothermal therapy. To construct a gold nanorod targeted delivery system for tumor a peptide substrate for urokinase-type plasminogen activator (uPA), expressed specifically on malignant tumors, was inserted between the PEG chain and the surface of the gold nanorods. In other words, we constructed PEG-peptide-modified gold nanorods. After mixing the gold nanorods with uPA, the PEG chain was released from the surface of the gold and subsequently nanorod aggregation took place. The formation of the aggregation was monitored as a decrease in light absorption at 900 nm. Tumor homogenate induced a significant decrease in this absorption. Larger amount of the PEG-peptide-modified gold nanorods bound to cells expressing uPA in vitro compared with control gold nanorods, which had scrambled sequence of the peptide. The PEG-peptide-modified gold nanorods showed higher accumulation in tumor than the control after they were injected intravenously into tumor-bearing mice, however, the density of the peptide on the surface of the gold nanorods was a key factor of their biodistributions. This targeted delivery system, which responds to uPA activity, is expected to be a powerful tool for tumor bioimaging and photothermal tumor therapy. (C) 2010 Elsevier Ltd. All rights reserved.