Gold nanoparticle-fluorophore complex for conditionally fluorescing signal mediator.
Gold nanoparticle-fluorophore complex for conditionally fluorescing signal mediator.
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DOI：
10.1016/j.aca.2011.03.058
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发表时间：
2011-06
影响因子：
6.2
通讯作者：
Jianting Wang;S. Achilefu;M. Nantz;K. Kang
中科院分区：
文献类型：
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作者：
Jianting Wang;S. Achilefu;M. Nantz;K. Kang
具有高特异性和灵敏度的荧光造影剂对于准确的疾病检测和诊断是有价值的。球形金纳米粒子（GNP）可以巧妙地用于开发高效的药剂。它们表面上的强电磁（等离子体）场可以非常有效地影响荧光团的电子，从而操纵荧光输出（即，猝灭或增强）。荧光猝灭可用于负传感，或用于条件去猝灭以增加特异性。荧光增强允许感测更灵敏。荧光改变的水平取决于GNP大小、荧光团的激发和发射波长和量子产率以及GNP和荧光团之间的距离。为了解GNP对荧光的影响机制，我们对常用荧光团的荧光变化参数进行了理论分析，重点研究了GNP对荧光的猝灭作用，结果表明，GNP对激发（Ex）和发射（Ex）波长接近GNP共振峰的荧光团的荧光有显著的猝灭作用。对于那些发射红色或近红外荧光的荧光团，为了实现猝灭，GNP和荧光团之间的距离需要非常短。一般来说，较短的距离导致更多的淬火。更大的GNP需要更短的距离来实现相同的淬灭水平。具有较低量子产率的荧光团的荧光（特别是具有远红或近红外发射的荧光团）更难以被GNP猝灭（需要非常短的距离）。在理论研究的基础上，我们研制了一种近红外造影剂，通过短肽间隔物与CYP缀合。通常Cypate的荧光被猝灭。间隔区具有尿激酶型纤溶酶原激活物（uPA;癌症分泌酶）的底物基序。该造影剂仅在uPA存在的情况下发射荧光，其中uPA切割间隔区。这种设计可用于表征癌症类型，也可用于诊断具有特征酶的其他疾病。
Fluorescent contrast agents with high specificity and sensitivity are valuable for accurate disease detection and diagnosis. Spherical gold nanoparticles (GNPs) can be smartly utilized for developing highly effective agents. The strong electromagnetic (plasmon) field on their surface can be very effective in influencing the electrons of fluorophores and, thus, manipulating the fluorescence output (i.e., either quenching or enhancement). Fluorescence quenching can be used for negative sensing, or for conditional de-quenching to increase the specificity. Fluorescence enhancement allows sensing to be more sensitive. The level of fluorescence alteration depends on the GNP size, the excitation and emission wavelengths and quantum yield of the fluorophore, and the distance between the GNP and the fluorophore. To understand the mechanisms of the fluorescence change by GNP, we have theoretically analyzed the parameters involved in the fluorescence alteration for commonly used fluorophores, with an emphasis on quenching.The results showed that the fluorescence of fluorophores with the excitation (Ex) and emission (Ex) wavelengths close to the GNP resonance peak tended to be significantly quenched by GNPs. For those fluorophores emitting fluorescence in red or near infrared, to achieve quenching, the distance between GNP and the fluorophore was required to be very short. In general, a shorter distance resulted in more quenching. Bigger GNPs require a shorter distance to achieve the same level of quenching. The fluorescence of a fluorophore with a lower quantum yield (especially the one with emission in far-red or near-infrared) is more difficult to be quenched by GNPs (requires very short distance). Instead, it can be enhanced.Based on the theoretical study, we have developed a near-infrared contrast agent, i.e., Cypate conjugated GNPviaa short peptide spacer. Normally the fluorescence of Cypate was quenched. The spacer has a motif of a substrate for urokinase type plasminogen activator (uPA; cancer-secreting enzyme). This contrast agent emits fluorescence only in the presence of uPA, where the uPA cleaves the spacer. This design can be used in characterization of the cancer type and also in diagnosing other diseases with signature enzymes.