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A Janus-like DNA probekit for simultaneously imaging the homo- and heterodimerization of HER2 and HER3 on living tumor cells
Sensors and Actuators B: Chemical ( IF 8.0 ) Pub Date : 2021-10-08 , DOI: 10.1016/j.snb.2021.130872
Ailing Kan 1 , Shengyong Ding 2 , Nan Zhang 3 , Wei Jiang 1
Affiliation  

HER2:HER2 homodimer and HER2:HER3 heterodimer are crucial participants and complicatedly interrelated in tumor progression and therapy. Here, we construct a Janus-like DNA probekit for simultaneously monitoring them on tumor cells. In this probekit, HER2 aptamer with a cytosine-rich stretch extended (Apt2-C) is labeled with FRET donor AF488 and acceptor AF594 at a distance apart; HER3 aptamer with a guanine-rich stretch extended (Apt3-G) is labeled with another FRET acceptor Cy3. Apt2-C and Apt3-G bind to HER2 and HER3 via their aptamers, respectively. Along with homodimerized HER2, two cytosine-rich stretches within Apt2-C are nearer and fold into a bimolecular i-motif, narrowing AF488 and AF594 to germinate FRET for homodimerization indication. Upon HER2:HER3 heterodimerization, Apt2-C and Apt3-G are closer and hybridize on the cytosine-rich and guanine-rich stretches to trigger FRET between AF488 and Cy3 to indicate the heterodimerization. This probekit possesses Janus-like interactions as Apt2-C can interact with both identical Apt2-C and heterogenous Apt3-G, highly similar to the case that HER2 can both homodimerize identical HER2 and heterodimerize HER3. The probekit’s signals were well matched with HER2:HER2 homodimerization and HER2:HER3 heterodimerization, enabling more accurate monitoring of them on living tumor cells, offering a potential tool for related tumor assessment and medication.



中文翻译:

一种类似 Janus 的 DNA 探针试剂盒,用于同时对活肿瘤细胞上 HER2 和 HER3 的同二聚体和异二聚体进行成像

HER2:HER2 同源二聚体和 HER2:HER3 异源二聚体是至关重要的参与者,并且在肿瘤进展和治疗中相互复杂。在这里,我们构建了一个类似 Janus 的 DNA 探针套件,用于在肿瘤细胞上同时监测它们。在该探针套件中,带有富胞嘧啶延伸段的 HER2 适体 (Apt2-C) 以相距一定距离的 FRET 供体 AF488 和受体 AF594 标记;带有富含鸟嘌呤的延伸段 (Apt3-G) 的 HER3 适体被另一个 FRET 受体 Cy3 标记。Apt2-C 和 Apt3-G 分别通过适体与 HER2 和 HER3 结合。与同源二聚化的 HER2 一起,Apt2-C 内的两个富含胞嘧啶的片段更近并折叠成双分子 i-基序,缩小 AF488 和 AF594 以萌发 FRET 以指示同源二聚化。在 HER2:HER3 异源二聚化后,Apt2-C 和 Apt3-G 更接近并在富含胞嘧啶和富含鸟嘌呤的延伸段上杂交以触发 AF488 和 Cy3 之间的 FRET 以指示异二聚化。该探针套件具有类似 Janus 的相互作用,因为 Apt2-C 可以与相同的 Apt2-C 和异源的 Apt3-G 相互作用,这与 HER2 可以将相同的 HER2 同二聚化和异源二聚化的情况非常相似。该探针套件的信号与 HER2:HER2 同源二聚化和 HER2:HER3 异源二聚化良好匹配,能够更准确地监测它们对活肿瘤细胞的监测,为相关肿瘤评估和药物治疗提供了潜在工具。这与 HER2 可以将相同的 HER2 同二聚化和异二聚化 HER3 的情况非常相似。该探针套件的信号与 HER2:HER2 同源二聚化和 HER2:HER3 异源二聚化良好匹配,能够更准确地监测它们对活肿瘤细胞的监测,为相关肿瘤评估和药物治疗提供了潜在工具。这与 HER2 可以将相同的 HER2 同二聚化和异二聚化 HER3 的情况非常相似。该探针套件的信号与 HER2:HER2 同源二聚化和 HER2:HER3 异源二聚化良好匹配,能够更准确地监测它们对活肿瘤细胞的监测,为相关肿瘤评估和药物治疗提供了潜在工具。

更新日期:2021-10-13
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