An Activity-Based Nanosensor for Minimally-Invasive Measurement of Protease Activity in Traumatic Brain Injury

被引:6
|
作者
Kudryashev, Julia A. A. [1 ]
Madias, Marianne I. I. [1 ]
Kandell, Rebecca M. M. [1 ]
Lin, Queenie X. X. [1 ]
Kwon, Ester J. J. [1 ]
机构
[1] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
calpain-1; diagnostic; GFAP; hyaluronic acid; peptides; sex-dependent; targeting ligands; CONTROLLED CORTICAL IMPACT; EXTRACELLULAR-MATRIX; NANOPARTICLE; BIOMARKERS; CALPAIN; NEURODEGENERATION; DIAGNOSTICS; GENERATION; RETENTION; INCREASES;
D O I
10.1002/adfm.202300218
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Current screening and diagnostic tools for traumatic brain injury (TBI) have limitations in sensitivity and prognostication. Aberrant protease activity is a central process that drives disease progression in TBI and is associated with worsened prognosis, thus direct measurements of protease activity can provide more diagnostic information. In this study, a nanosensor is engineered to release a measurable signal into the blood and urine in response to activity from the TBI-associated protease calpain. Readouts from the nanosensor are designed to be compatible with ELISA and lateral flow assays, clinically-relevant assay modalities. In a mouse model of TBI, the nanosensor sensitivity is enhanced when ligands that target hyaluronic acid are added. In evaluation of mice with mild or severe injuries, the nanosensor identifies mild TBI with a higher sensitivity than the biomarker glial fibrillary acidic protein (GFAP). This nanosensor technology allows for measurement of TBI-associated proteases without the need to directly access brain tissue and has the potential to complement existing TBI diagnostic tools.
引用
收藏
页数:12
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