组会讲课人员:唐丹丹
Renalclearablepolyfluorophorenanosensors for earlydiagnosisofcancer and allograft rejection
肾脏可清除的多荧光团纳米传感器,用于早期诊断癌症和同种异体移植物排斥反应
主讲人:唐丹丹
Nature Materials |April 2022 | Volume21,Issue 5| 598-607|DOI: 10.1038/s41563-022-01224-2
Abstract:
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.
摘要:
光学纳米颗粒是一种很有前途的诊断工具;然而,它们的浅层光学成像深度和缓慢的人体清除率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-分子的药代动力学转换和近红外荧光开启反应。可激活的多荧光团纳米传感器可以在疾病部位积累,并与疾病相关的蛋白酶反应,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将肾脏可清除的荧光片段释放出来,用于无创纵向尿液分析,优于金标准血液和尿液分析,提供了与侵入性活检和流式细胞术分析相比较的敏感性和特异性水平。在啮齿类动物模型中,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1.6mm),并早期诊断急性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以通过一个简单的尿检应用于一系列疾病的早期诊断。