Renal clearable catalytic gold nanoclusters for in vivo disease monitoring
Renal clearable catalytic gold nanoclusters for in vivo disease monitoring
复制标题
DOI：
10.1038/s41565-019-0527-6
复制
发表时间：
2019-09-01
影响因子：
38.3
通讯作者：
Stevens, Molly M.
中科院分区：
文献类型：
--
作者：
Loynachan, Colleen N.;Soleimany, Ava P.;Stevens, Molly M.
超小的金纳米团簇(AuNC)由于具有特殊的肿瘤聚集和高效的肾脏清除特性，已成为活体成像的灵活探针。然而，其固有的催化活性，可以提高检测灵敏度，尚未被探索用于体内检测。通过利用AuNC的过氧化物酶模拟活性和肾脏的精确纳米级过滤，我们设计了多功能蛋白酶纳米传感器，可以对疾病微环境做出反应，在不到一小时的时间内产生直接比色的尿液读数。我们监测了结直肠癌小鼠模型收集的尿液中AuNCs的催化活性，在该模型中，荷瘤小鼠的比色信号比健康小鼠增加了13倍。纳米传感器在注射后四周内通过肝脏和肾脏排泄完全消除，没有毒性证据。我们设想，这种模块化方法将通过利用疾病的特定酶标记来实现对各种疾病的快速检测。
Ultrasmall gold nanoclusters (AuNCs) have emerged as agile probes for in vivo imaging, as they exhibit exceptional tumour accumulation and efficient renal clearance properties. However, their intrinsic catalytic activity, which can enable an increased detection sensitivity, has yet to be explored for in vivo sensing. By exploiting the peroxidase-mimicking activity of AuNCs and the precise nanometre-size filtration of the kidney, we designed multifunctional protease nanosensors that respond to disease microenvironments to produce a direct colorimetric urinary readout of the disease state in less than one hour. We monitored the catalytic activity of AuNCs in the collected urine of a mouse model of colorectal cancer in which tumour-bearing mice showed a 13-fold increase in colorimetric signal compared to healthy mice. The nanosensors were eliminated completely through hepatic and renal excretion within four weeks of injection with no evidence of toxicity. We envision that this modular approach will enable the rapid detection of a diverse range of diseases by exploiting their specific enzymatic signatures.