State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Molecular Recognition and Biosensing, Frontiers Science Centers for Cell Responses and New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China.
Key Laboratory of Inorganic-Organic Hybrid Functional Materials Chemistry, Ministry of Education, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Tianjin Normal University, Tianjin 300387, China.
ACS Nano. 2024 Jun 25;18(25):16113-16125. doi: 10.1021/acsnano.4c00280. Epub 2024 Jun 10.
Urinary extracellular vesicles (uEVs) are regarded as highly promising liquid-biopsy biomarkers for the early diagnosis and prognosis of bladder cancer (BC). However, detection of uEVs remains technically challenging owing to their huge heterogeneity and ultralow abundance in real samples. We herein present a choline phosphate-grafted platinum nanozyme (Pt@CP) that acts as a universal EV probe for the construction of a high-throughput and high-sensitivity immunoassay, which allowed multiplex profiling of uEV protein markers for BC detection. With the Pt@CP-based immunoassays, three uEV protein markers (MUC-1, CCDC25, and GLUT1) were identified for BC, by which the BC cases ( = 48), cystitis patients ( = 27), and healthy donors ( = 24) were discriminated with high clinical sensitivity and specificity (area under curve = 98.3%). For the BC cases ( = 9) after surgery, the Pt@CP-based immunoassay could report the postoperative residual tumor that cannot be observed by cystoscopy, which is clinically significant for assessing BC recurrence. This work provides generally high sensitivity for EV detection, facilitating the discovery and clinical use of EV-based biomarkers.
尿液细胞外囊泡 (uEVs) 被认为是极具前景的膀胱癌 (BC) 早期诊断和预后的液体活检生物标志物。然而，由于其在真实样本中巨大的异质性和超低丰度，uEV 的检测仍然具有技术挑战性。我们在此提出了一种磷酸胆碱接枝的铂纳米酶 (Pt@CP)，它可以作为一种通用的 EV 探针，用于构建高通量和高灵敏度的免疫分析，从而可以对 uEV 蛋白标志物进行多重分析，以用于 BC 的检测。通过基于 Pt@CP 的免疫分析，我们鉴定了三种用于 BC 的 uEV 蛋白标志物 (MUC-1、CCDC25 和 GLUT1)，利用这些标志物可以区分 BC 病例 ( = 48)、膀胱炎患者 ( = 27) 和健康供体 ( = 24)，具有较高的临床灵敏度和特异性 (曲线下面积 = 98.3%)。对于手术后的 BC 病例 ( = 9)，基于 Pt@CP 的免疫分析可以报告膀胱镜无法观察到的术后残留肿瘤，这对于评估 BC 复发具有重要的临床意义。这项工作为 EV 的检测提供了普遍较高的灵敏度，有利于 EV 生物标志物的发现和临床应用。
