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Ultrasmall visible-to-near-infrared emitting silver- sulflde quantum dots for cancer detection and imaging

机译:超小型可见到近红外发射的硫化银量子点,用于癌症检测和成像

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The large size of many near infrared (NIR) fluorescent nanoparticles prevents rapid extravasation from blood vessels and subsequent diffusion to tumors. This confines in vivo uptake to the peritumoral space and results in high liver retention. We developed a viscosity modulated approach to synthesize ultrasmall silver sulfide quantum dots (QDs) with distinct tunable light emission from visible to near-infrared in spectrum and a QD core diameter between less than 5 nm. Further functionalization of these Ag_2S QDs with different type of molecules such as targeting peptides, retains monodisperse, relatively small water soluble QDs without loss of the functionality of the peptide's high binding affinity to cancerous tumor. Fluorescence and electron microscopy showed that selective integrin-mediated internalization was observed only in cancer cells treated with the peptide-labeled QDs, demonstrating that the unlabeled hydrophilic nanoparticles exhibit characteristics of negatively charged fluorescent dye molecules, which typically do not internalize in cells. The biodistribution profiles of intravenously administered QDs in different mouse models of cancer reveal an exceptionally high tumor-to-liver uptake ratio, suggesting that the small sized QDs evaded conventional opsonization and subsequent high uptake in the liver and spleen. The seamless tunability of the QDs over a wide spectral range with only a small increase in size, as well as the ease of labeling the bright and non-cytotoxic QDs with biomolecules, provides a platform for multiplexing information, tracking the trafficking of single molecules in cells, and selectively targeting disease biomarkers in living organisms without premature QD opsonization in circulating blood.
机译:许多近红外(NIR)荧光纳米粒子的大尺寸阻止了从血管的快速外渗以及随后扩散到肿瘤中。这限制了体内对肿瘤周围空间的摄取,并导致较高的肝retention留。我们开发了一种粘度调制方法来合成超小型硫化银量子点(QD),该量子点具有从可见光到近红外光谱的明显可调光,并且QD核心直径小于5 nm。这些Ag_2S QD用不同类型的分子(例如靶向肽)进一步功能化,可保留单分散的相对较小的水溶性QD,而不会丧失该肽对癌性肿瘤的高结合亲和力的功能。荧光和电子显微镜显示,仅在用肽标记的量子点处理的癌细胞中观察到选择性整联蛋白介导的内在化,这表明未标记的亲水性纳米粒子表现出带负电的荧光染料分子的特征,该特征通常不会在细胞内内化。在不同的癌症小鼠模型中静脉内施用的QD的生物分布特征显示出异常高的肿瘤-肝脏摄取率,这表明小尺寸的QD避免了常规的调理作用,并随后在肝脏和脾脏中大量摄取。 QD在很宽的光谱范围内的无缝可调性,其尺寸仅增加了一点点,并且易于用生物分子标记明亮的且无细胞毒性的QD,从而提供了一个用于多路复用信息,跟踪单分子运输的平台。细胞,并选择性靶向活生物体中的疾病生物标记物,而不会在循环血液中过早进行QD调理作用。

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