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Point-of-care non-invasive enzyme-cleavable nanosensors for acute transplant rejection detection
Biosensors and Bioelectronics ( IF 12.6 ) Pub Date : 2022-07-13 , DOI: 10.1016/j.bios.2022.114568
Shi-Jie Liu 1 , Ke Ma 2 , Long-Shan Liu 1 , Ke Wang 2 , Ying-Ao Zhang 2 , Zi-Rong Bi 1 , Yan-Xu Chen 1 , Ke-Zheng Chen 2 , Chang-Xi Wang 1 , Sheng-Lin Qiao 2
Affiliation  

Accurate and non-invasive monitoring of allograft posttransplant is essential for early detection of acute cellular rejection and determines the long-term survival of the graft. Clinically, tissue biopsy is the most effective approach for diagnosing transplant rejection. Nonetheless, the procedure is invasive and potentially triggers organ failure. This work aims to design and apply GzmB-responsive nanosensors (GBRNs) that can readily size-change in graft tissues. Subsequently, we investigate the activity of serine protease granzyme B by generating a direct colorimetric urinary readout for non-invasive detection of transplant rejection in under 1 h. In preclinical heart graft mice models of transplant rejection, GBRNs were cleaved by GzmB and excreted by the kidneys via accurate nanometre-size glomerular filtration. By exploiting the catalytic activity of ultrasmall gold nanoclusters, GBRNs urinalysis promotes ultrasensitive surveillance of rejection episodes with a receiver operator characteristic curve area under the curve of 0.896 as well as a 95% confidence interval of about 0.7701–1.000. Besides, the catalytic activity of gold nanoclusters in urine can be detected at point-of-care testing to predict the immunity responses in mice with insufficient immunosuppressive therapy. Therefore, this non-invasive, sensitive, and quantitative method is a robust and informative approach for rapid and routine monitoring of transplant allografts without invasive biopsy.



中文翻译:

用于急性移植排斥检测的即时非侵入性酶可切割纳米传感器

移植后对同种异体移植物进行准确和非侵入性监测对于早期发现急性细胞排斥反应至关重要,并决定移植物的长期存活率。临床上,组织活检是诊断移植排斥反应最有效的方法。尽管如此,该程序是侵入性的,并可能引发器官衰竭。这项工作旨在设计和应用GzmB 响应纳米传感器 (GBRN),该传感器可以很容易地改变移植组织的大小。随后,我们通过生成直接比色尿液读数来研究丝氨酸蛋白酶颗粒酶 B 的活性,以便在 1 小时内无创检测移植排斥反应。在移植排斥的临床前心脏移植小鼠模型中,GBRNs 被 GzmB 切割通过肾脏排泄精确的纳米级肾小球滤过。通过利用超小金纳米簇的催化活性,GBRNs 尿液分析促进了对排斥事件的超灵敏监测,其曲线下的接受者操作特征曲线面积为 0.896,95% 置信区间约为 0.7701-1.000。此外,尿液中金纳米簇的催化活性可以在即时检测中检测到,以预测免疫抑制治疗不足的小鼠的免疫反应。因此,这种非侵入性、灵敏和定量的方法是一种可靠且信息丰富的方法,可用于快速和常规监测同种异体移植物而无需侵入性活检。

更新日期:2022-07-16
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