Sustained-Release Synthetic Biomarkers for Monitoring Thrombosis and Inflammation Using Point-of-Care Compatible Readouts

• Published in: Advanced functional materials Vol. 26; no. 17; pp. 2919 - 2928
• Main Authors: Dudani, Jaideep S., Buss, Colin G., Akana, Reid T. K., Kwong, Gabriel A., Bhatia, Sangeeta N.
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 03.05.2016
• Subjects: Biomarkers; bionanotechnology; Disease control; Monitoring; Nanostructure; Protease; protease sensors; Sensors; subcutaneous delivery; Thrombosis; urinary diagnostics; Urinary diagnostics; Protease sensors; Subcutaneous delivery; Bionanotechnology
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201505142

Postoperative infection and thromboembolism represent significant sources of morbidity and mortality but cannot be easily tracked after hospital discharge. Therefore, a molecular test that could be performed at home would significantly impact disease management. The laboratory has previously developed intravenously delivered “synthetic biomarkers” that respond to dysregulated proteases to produce a urinary signal. These assays, however, have been limited to chronic diseases or acute diseases initiated at the time of diagnostic administration. Here, a subcutaneously administered sustained‐release system, using small poly(ethylene glycol) scaffolds (<10 nm) to promote diffusion into the bloodstream over a day, is formulated. The utility of a thrombin sensor to identify thrombosis and an Matrix metalloproteinase (MMP) sensor to measure inflammation is demonstrated. Finally, a companion paper ELISA (Enzyme‐linked immunosorbent sssay), using printed wax barriers, with nanomolar sensitivity for urinary reporters for point‐of‐care detection is developed. The approach for subcutaneous delivery of nanosensors combined with urinary paper analysis may enable facile monitoring of at‐risk patients. Subcutaneous injections of PEG‐chaperoned protease sensors enter the bloodstream efficiently over several hours, traverse the host vasculature, and respond to disease‐associated proteases. Fragments shed from the sensor are excreted into urine and detected by a paper test to enable extended monitoring of disease burden.