Selective targeting of antibody conjugated multifunctional nanoclusters (nanoroses) to epidermal growth factor receptors in cancer cells.
Selective targeting of antibody conjugated multifunctional nanoclusters (nanoroses) to epidermal growth factor receptors in cancer cells.
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DOI：
10.1021/la200659z
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发表时间：
2011-06-21
期刊：
影响因子：
--
通讯作者：
Johnston KP
中科院分区：
文献类型：
--
作者：
Ma LL;Tam JO;Willsey BW;Rigdon D;Ramesh R;Sokolov K;Johnston KP
小于100 nm的抗体(Ab)纳米颗粒能够靶向和调节特定细胞类型的生物学，这可能使细胞成像和癌症治疗方面的重大进展成为可能。一个关键的挑战是将高度的靶向、成像和治疗功能加载到小而稳定的颗粒中。在我们之前的研究中，我们开发了一种通用的方法，称为衬底薄自催化生长(TAG)，在氧化铁纳米团簇核心上形成超薄的不对称金涂层，产生特殊的近红外(NIR)吸收。AlexaFluor 488标记的抗体被用来关联与氧化铁/金纳米簇(纳米颗粒)结合的抗体的数量与流体力学尺寸的关系。观察到54个Abs在纳米糖表面由亚单层向多层聚集体转变，总粒径约为60~65 nm。流体力学直径表明覆盖了54个抗体的单层，与几何模型的预测一致，假设每个抗体分子的圆形足迹为16.9 nm直径。采用暗视野显微镜和原子吸收光谱(AAS)分析方法，研究了与表皮生长因子受体(EGFR)特异性单抗偶联的纳米团簇在A431癌细胞中的靶向效应。由于纳米团簇在细胞中的高摄取和单个纳米团簇的高本征近红外吸收，获得了强烈的近红外散射。暗场反射显微镜和荧光显微镜的双模成像表明，Abs在被癌细胞摄取后仍然附着在Au表面。能够加载强烈的多功能，特别是强近红外吸收，结合抗体单层，以及以前证明的总颗粒仅为63 nm的强R2 MRI对比度，是开发用于结合分子特异性成像和治疗的治疗药物的重要一步。
The ability of smaller than 100 nm antibody (Ab) nanoparticle conjugates to target and modulate the biology of specific cell types may enable major advancements in cellular imaging and therapy in cancer. A key challenge is to load a high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. A versatile method called thin autocatalytic growth on substrate (TAGs) has been developed in our previous study to form ultra-thin and asymmetric gold coatings on iron oxide nanocluster cores producing exceptional near infrared (NIR) absorbance. AlexaFluor 488 labeled Abs were used to correlate the number of Abs conjugated to iron oxide/gold nanoclusters (nanoroses) with the hydrodynamic size. A transition from sub-monolayer to multilayer aggregates of Abs on the nanorose surface was observed for 54 Abs and an overall particle diameter of ~60 to 65 nm. The hydrodynamic diameter indicated coverage of a monolayer of 54 Abs, in agreement with the prediction of a geometric model, by assuming a circular footprint of 16.9 nm diameter per Ab molecule. The targeting efficacy of nanoclusters conjugated with monoclonal Abs specific for epidermal growth factor receptor (EGFR) was evaluated in A431 cancer cells using dark field microscopy and atomic absorbance spectrometry (AAS) analysis. Intense NIR scattering was achieved from both high uptake of nanoclusters in cells and high intrinsic NIR absorbance of individual nanoclusters. Dual mode imaging with dark field reflectance microscopy and fluorescence microscopy indicates the Abs remained attached to the Au surfaces upon the uptake by the cancer cells. The ability to load intense multifunctionality, specifically strong NIR absorbance, conjugation of an Ab monolayer in addition to a strong r2 MRI contrast that was previously demonstrated in a total particle size of only 63 nm, is an important step forward in development of theranostic agents for combined molecular specific imaging and therapy.
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DOI：
10.1073/pnas.2232479100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Hirsch, LR;Stafford, RJ;West, JL
通讯作者：
West, JL
影响因子：
38.3
作者：
Dames, Petra;Gleich, Bernhard;Rudolph, Carsten
通讯作者：
Rudolph, Carsten
影响因子：
38.3
作者：
Jiang, Wen;Kim, Betty Y. S.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.
影响因子：
17.1
作者：
Hu, Ying;Noelck, Sterling J.;Drezek, Rebekah A.
通讯作者：
Drezek, Rebekah A.
影响因子：
10.8
作者：
Bagalkot, Vaishali;Zhang, Liangfang;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.