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

摘要

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.