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Reversible and Highly Ordered Biointerfaces for Efficient Capture and Nondestructive Release of Circulating Tumor Cells
Analytical Chemistry ( IF 6.7 ) Pub Date : 2022-06-22 , DOI: 10.1021/acs.analchem.2c01743
Siyi Wang 1 , Jiasen Cui 2 , Qian Fan 1, 3 , Jiaxing Gan 2 , Chunran Liu 2 , Yuanhe Wang 4 , Ting Yang 1 , Jianhua Wang 1 , Chaoyong Yang 3, 5
Affiliation  

The engineering strategy of artificial biointerfaces is vital for governing their performances in bioanalysis and diagnosis. Highly ordered arrangement of affinity ligands on the interface surface facilitates efficient interaction with target molecules, whereas biointerfaces aimed at drug delivery or rare cell isolation require sophisticated stimuli-response mechanisms. However, it is still challenging to facilely fabricate biointerfaces possessing the two features. Herein, we endow a biointerface with both reversibility and capability to orderly assemble affinity ligands by introducing boronic acid moieties alone. By boronate conjugation via glycosylation sites, avidin was well arranged at the surface of boronic acid-decorated carbon nitride nanosheets for the assembly of biotinylated aptamers. The ordered orientation of aptamers largely relieved their inactivation caused by inter-strand entanglement, facilitating significant increase in cell affinity for the isolation of circulating tumor cells (CTCs). The reversible boronate conjugation also facilitated mild release of CTCs by acid fructose with high cell viability. This engineered interface was capable of isolating CTCs from the peripheral blood of tumor-bearing mice and cancer patients. The successful utilization of the isolated CTCs in the downstream drug susceptibility test and mutation analysis demonstrated the clinical potential of this biointerface for the early diagnosis of cancers and precision medicine.

中文翻译:

用于循环肿瘤细胞高效捕获和无损释放的可逆且高度有序的生物界面

人工生物界面的工程策略对于控制其在生物分析和诊断中的性能至关重要。界面表面亲和配体的高度有序排列有助于与靶分子的有效相互作用,而针对药物递送或稀有细胞分离的生物界面需要复杂的刺激反应机制。然而,轻松制造具有这两个特征的生物界面仍然具有挑战性。在此,我们通过单独引入硼酸部分赋予生物界面可逆性和有序组装亲和配体的能力。通过糖基化位点的硼酸盐共轭,抗生物素蛋白很好地排列在硼酸修饰的氮化碳纳米片的表面,用于组装生物素化的适体。适体的有序取向在很大程度上缓解了它们由链间缠结引起的失活,促进细胞亲和力显着增加,以分离循环肿瘤细胞 (CTC)。可逆的硼酸盐共轭还促进了具有高细胞活力的酸性果糖温和释放 CTC。这种工程化界面能够从荷瘤小鼠和癌症患者的外周血中分离出 CTC。在下游药敏试验和突变分析中成功利用分离的 CTC,证明了这种生物界面在癌症早期诊断和精准医疗方面的临床潜力。可逆的硼酸盐共轭还促进了具有高细胞活力的酸性果糖温和释放 CTC。这种工程化界面能够从荷瘤小鼠和癌症患者的外周血中分离出 CTC。在下游药敏试验和突变分析中成功利用分离的 CTC,证明了这种生物界面在癌症早期诊断和精准医疗方面的临床潜力。可逆的硼酸盐共轭还促进了具有高细胞活力的酸性果糖温和释放 CTC。这种工程化界面能够从荷瘤小鼠和癌症患者的外周血中分离出 CTC。在下游药敏试验和突变分析中成功利用分离的 CTC,证明了这种生物界面在癌症早期诊断和精准医疗方面的临床潜力。
更新日期:2022-06-22
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