Highly Fluorescent Dye-Doped Silica Nanoparticles Increase Flow Cytometry Sensitivity for Cancer Cell Monitoring
Highly Fluorescent Dye-Doped Silica Nanoparticles Increase Flow Cytometry Sensitivity for Cancer Cell Monitoring
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DOI：
10.1007/s12274-009-9041-8
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发表时间：
2009-06-01
期刊：
影响因子：
9.9
通讯作者：
Tan, Weihong
中科院分区：
文献类型：
--
作者：
Estevez, M. -Carmen;O'Donoghue, Meghan B.;Tan, Weihong
癌症的早期准确诊断和治疗有赖于对肿瘤细胞的快速、灵敏和选择性检测。目前对癌症，特别是白血病的诊断依赖于组织学和使用单一染料标记抗体的流式细胞术。然而，这种结合可能不会导致高信号输出，这可能会阻碍检测，特别是当探针具有相对较弱的亲和力或当受体在靶细胞表面以低浓度表达时。为了解决这些问题，我们开发了一种使用染料掺杂二氧化硅纳米颗粒(NPs)灵敏而快速地检测癌细胞的新方法，与标准方法相比，该方法将流式细胞仪分析中的检测灵敏度提高了10到100倍。我们的纳米颗粒大小类似于60纳米，可以在基质中包裹数千个单独的染料分子。我们已经广泛地研究了表面修饰策略，以使纳米粒子适合于利用流式细胞仪选择性地检测癌细胞。NPs用聚乙二醇(PEG)功能化，以防止非特异性相互作用，并与中性亲和素官能化，以允许与生物素化分子的普遍结合。凭借其对靶癌细胞的可靠和选择性检测，这些纳米粒子在传统的流式细胞术中显示出了良好的应用前景。此外，它们表现出低背景信号、高信号增强和有效的功能化，无论是抗体靶向还是适配子靶向。
Early and accurate diagnosis and treatment of cancer depend on rapid, sensitive, and selective detection of tumor cells. Current diagnosis of cancers, especially leukemia, relies on histology and flow cytometry using single dye-labeled antibodies. However, this combination may not lead to high signal output, which can hinder detection, especially when the probes have relatively weak affinities or when the receptor is expressed in a low concentration on the target cell surface. To solve these problems, we have developed a novel method for sensitive and rapid detection of cancer cells using dye-doped silica nanoparticles (NPs) which increases detection sensitivity in flow cytometry analyses between 10- and 100-fold compared to standard methods. Our NPs are similar to 60 nm in size and can encapsulate thousands of individual dye molecules within their matrix. We have extensively investigated surface modification strategies in order to make the NPs suitable for selective detection of cancer cells using flow cytometry. The NPs are functionalized with polyethylene glycol (PEG) to prevent nonspecific interactions and with neutravidin to allow universal binding with biotinylated molecules. By virtue of their reliable and selective detection of target cancer cells, these NPs have demonstrated their promising usefulness in conventional flow cytometry. Moreover, they have shown low background signal, high signal enhancement, and efficient functionalization, either with antibody- or aptamer-targeting moieties.