Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging
Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging
复制标题
DOI：
10.1088/0957-4484/21/5/055103
复制
发表时间：
2010-02-05
期刊：
影响因子：
3.5
通讯作者：
Koyakutty, Manzoor
中科院分区：
文献类型：
--
作者：
Retnakumari, Archana;Setua, Sonali;Koyakutty, Manzoor
报道了叶酸受体阳性口腔癌细胞的分子受体靶向成像，其使用叶酸缀合的荧光Au 25纳米簇（Au NCs）。以牛血清白蛋白（BSA）为稳定剂，采用绿色化学还原剂抗坏血酸（维生素C）对Au+离子进行控制还原，合成了具有高荧光的Au 25团簇。对于癌细胞的基于靶向成像的检测，簇通过与BSA壳的酰胺键与叶酸（FA）缀合。生物缀合的簇在从4至14的宽pH范围内显示出优异的稳定性，并且在磷酸盐缓冲盐水（PBS）中在pH 7.4下的荧光效率类似于5.7%，表明在生物缀合反应和细胞簇相互作用期间血清白蛋白对纳米簇的有效保护。纳米团簇的物理化学性质，毒性和体外癌症靶向功效进行了表征。X射线光电子能谱（XPS）表明与金属Au 4f（7/2）相关的结合能类似于83.97 eV，与Au 4f（5/2）相关的结合能类似于87.768 eV。透射电子显微镜和原子力显微镜揭示了形成的单个纳米团簇的大小类似于1 nm和蛋白质簇聚集体的大小类似于8 nm。光致发光研究显示出明亮的荧光，其峰值最大值在674 nm附近，光谱分布覆盖近红外（NIR）区域，这使得在700-800 nm发射窗口（组织对光的吸收最小）对簇进行成像成为可能。细胞活力和活性氧毒性的研究表明，无毒的性质的Au集群高达相对较高的浓度为500 μ g ml（-1）。在FR+ve口腔鳞状细胞癌（KB）和乳腺癌细胞MCF-7上证明了使用Au簇的受体靶向癌症检测，其中发现与阴性对照细胞系相比，FA缀合的Au-25簇以显著更高的浓度内化。这项研究表明，使用无毒的荧光Au纳米簇的癌症的靶向成像的潜力。
Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au25 nanoclusters (Au NCs) is reported. Highly fluorescent Au25 clusters were synthesized by controlled reduction of Au+ ions, stabilized in bovine serum albumin (BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid (FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of similar to 5.7% at pH 7.4 in phosphate buffer saline (PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy (XPS) suggests binding energies correlating to metal Au 4f(7/2) similar to 83.97 eV and Au 4f(5/2) similar to 87.768 eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size similar to 1 nm and protein cluster aggregates of size similar to 8 nm. Photoluminescence studies show bright fluorescence with peak maximum at similar to 674 nm with the spectral profile covering the near-infrared (NIR) region, making it possible to image clusters at the 700-800 nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500 mu g ml(-1). Receptor-targeted cancer detection using Au clusters is demonstrated on FR+ve oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au-25 clusters were found internalized in significantly higher concentrations compared to the negative control cell lines. This study demonstrates the potential of using non-toxic fluorescent Au nanoclusters for the targeted imaging of cancer.