Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
J Am Chem Soc. 2021 Sep 22;143(37):15145-15151. doi: 10.1021/jacs.1c05674. Epub 2021 Sep 8.
Rapid and specific identification of tumor metabolic markers is of great significance. Herein, a convenient, reliable and specific strategy was proposed to screen prostate cancer (PCa) individuals through indirectly quantifying sarcosine, an early indicator of PCa, in the clinical urine samples. The success roots in the rational design of a cascade response model, which takes integrated sarcosine oxidase (SOX) as a specific recognition unit and oxygen-sensitive molecule as a signal reporter. The newly developed hierarchical mesoporous Zr-based metal-organic frameworks with continuously tunable mesopore size ensure the synergetic work of the SOX and response unit spatially separated in their neighboring mesoporous and microporous domains, respectively. The large mesopore up to 12.1 nm not only greatly enhances the loading capacity of SOX but also spares enough space for the free diffusion of sarcosine. On this basis, the probe is competent to specifically check out the tiny concentration change of sarcosine in the urine sample between PCa patients and healthy humans. Such a concept of enzyme-assisted substrate sensing could be simply extended by altering the type of immobilized enzymes, hopefully setting a guideline for the rational design of multiple probes to quantify specific biomarkers in complex biological samples.
快速、准确地鉴定肿瘤代谢标志物具有重要意义。在此,我们提出了一种简便、可靠、特异的策略,通过间接定量检测临床尿液样本中的肌氨酸(PCa 的早期标志物)来筛选前列腺癌(PCa)个体。该策略的成功源于级联反应模型的合理设计,该模型以整合的肌氨酸氧化酶(SOX)作为特异性识别单元,以氧敏分子作为信号报告器。新开发的具有连续可调介孔尺寸的分层介孔 Zr 基金属-有机骨架,确保 SOX 和响应单元在其相邻的介孔和微孔域中空间分离,协同工作。高达 12.1nm 的大介孔不仅大大提高了 SOX 的负载能力,而且为肌氨酸的自由扩散留出了足够的空间。在此基础上,该探针能够特异性地检测出 PCa 患者和健康人群尿液样本中肌氨酸的微小浓度变化。这种酶辅助底物传感的概念可以通过改变固定化酶的类型来简单扩展,有望为在复杂生物样本中定量特定生物标志物的多个探针的合理设计提供指导。