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Multiplex Imaging of Single Tumor Cells Using Quantum-Dot-Conjugated Aptamers

机译:使用量子点缀合的适体对单个肿瘤细胞的多重成像

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Although cancer originates from genetic abnormalities and subsequent changes at the molecular level, conventional medical imaging methods, including computed tomography (CT), magnetic resonance imaging (MRI), and even positron emission tomography with radiolabeled 2-fluoro-2-deoxy-Dglucose (FDG PET), assess only anatomical changes or nonspecific glucose metabolism. To diagnose cancer at an earlier stage, and to learn more about the basic mechanism associated with the development of cancer, molecular imaging to assess changes at the molecular and genetic levels is of great value.~[1] Antibodies have been widely used for targeting specific molecules, but this method has limitations that include possible immune reactions, long residence time in the blood, and difficulties in production.Anaptamer is a small oligonucleotide that binds to specific targets similarly to antibodies, but has advantages that include a lack of immunogenicity, small size,and ease of synthesis.~[2] Aptamers targeting cancer-specificproteins, such as vascular endothelial growth factor (VEGF), pigpen, prostate-specific membrane antigen (PSMA), and receptor tyrosine kinase (RTK), have been developed and studied to detect cancer.~[3–6] However, none of the studies using cancer biomarkers has attempted a simultaneous multiplex imaging approach by a single absorption source, which could provide detailed imaging information about cancer genetics in a single cancer cell. Fortunately, for the in vitro simultaneous multiplex imaging of cancers, various quantum dots (QDs) have been developed. QDs are promising imaging probes as they are capable of broad absorption with a narrow emission spectrum, high quantum yields, low photobleaching, and chemical stability. Furthermore, surface-modified QDs can easily be conjugated with ligands such as aptamer or peptides that specifically target biomolecules.~[7,8] Most of all, QDs conjugated with single-stranded DNA of an aptamer offer promising methods to assess the diverse genetic expression in a single cell by the demonstration of different colors.~[9–11]
机译:尽管癌症起源于遗传异常和分子水平的后续变化,但常规医学成像方法包括计算机断层扫描(CT),磁共振成像(MRI)甚至是带有放射性标记的2-氟-2-脱氧葡萄糖的正电子发射断层扫描( FDG PET),仅评估解剖变化或非特异性葡萄糖代谢。为了更早地诊断癌症并更多地了解与癌症发展相关的基本机制,分子成像在分子和遗传水平上评估变化具有重要价值。〜[1]抗体已广泛用于靶向适体是一种小的寡核苷酸,与抗体类似地结合到特定的靶标上,但具有缺乏免疫原性的优点,但这种方法具有局限性,包括可能的免疫反应,在血液中的长停留时间和生产困难。体积小,易于合成。[2]已开发出针对癌症特异性蛋白的适体,例如血管内皮生长因子(VEGF),猪圈,前列腺特异性膜抗原(PSMA)和受体酪氨酸激酶(RTK)。 [3-6]但是,没有一项使用癌症生物标记物的研究尝试通过单一吸收源同时进行多重成像方法,我们将提供有关单个癌细胞中癌症遗传学的详细成像信息。幸运的是,对于癌症的体外同时多重成像,已经开发了各种量子点(QD)。量子点是有前途的成像探针,因为它们能够以窄的发射光谱,高的量子产率,低的光漂白和化学稳定性被广泛吸收。此外,表面修饰的QD可以轻松地与配体(例如适体或特异性靶向生物分子的肽)偶联。〜[7,8]最重要的是,与aptamer的单链DNA偶联的QD提供了有希望的方法来评估多种遗传通过展示不同的颜色在单个细胞中表达。〜[9-11]

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