Optical nanoparticles are promising diagnostic tools; however, their shallow optical imaging depth and slow clearance from the body have impeded their use for in vivo disease detection. To address these limitations, we develop activatable polyfluorophore nanosensors with biomarker-triggered nanoparticle-to-molecule pharmacokinetic conversion and near-infrared fluorogenic turn-on response. Activatable polyfluorophore nanosensors can accumulate at the disease site and react with disease-associated proteases to undergo in situ enzyme-catalysed depolymerization. This disease-specific interaction liberates renal-clearable fluorogenic fragments from activatable polyfluorophore nanosensors for non-invasive longitudinal urinalysis and outperforms the gold standard blood and urine assays, providing a level of sensitivity and specificity comparable to those of invasive biopsy and flow cytometry analysis. In rodent models, activatable polyfluorophore nanosensors enable ultrasensitive detection of tumours (1.6 mm diameter) and early diagnosis of acute liver allograft rejection. We anticipate that our modular nanosensor platform may be applied for early diagnosis of a range of diseases via a simple urine test.

光学纳米粒子是有前途的诊断工具；然而，它们的光学成像深度浅和从体内清除缓慢阻碍了它们在体内疾病检测中的应用。为了解决这些限制，我们开发了可激活的多荧光团纳米传感器，具有生物标志物触发的纳米颗粒到分子的药代动力学转换和近红外荧光开启响应。可激活的多荧光团纳米传感器可以在疾病部位积聚并与疾病相关的蛋白酶发生反应，进行原位酶催化解聚。这种疾病特异性的相互作用从可激活的多荧光团纳米传感器中释放出肾脏可清除的荧光片段，用于非侵入性纵向尿液分析，并且优于金标准血液和尿液分析，提供与侵入性活检和流式细胞术分析相当的灵敏度和特异性。在啮齿动物模型中，可激活的多荧光团纳米传感器能够超灵敏地检测肿瘤（直径 1.6 毫米）并早期诊断急性同种异体肝移植排斥反应。我们预计我们的模块化纳米传感器平台可用于通过简单的尿液测试来早期诊断一系列疾病。