Journal
ADVANCED HEALTHCARE MATERIALS
Volume 11, Issue 11, Pages -Publisher
WILEY
DOI: 10.1002/adhm.202102685
Keywords
activity-based nanosensors; drug delivery; ionic liquids; nanoparticles; protease; thrombosis; transdermal delivery
Funding
- Koch Institute Marble Center for Cancer Nanomedicine
- Koch Institute from the National Cancer Institute (Swanson Biotechnology Center) [P30-CA14051]
- National Institute of Environmental Health Sciences [P30-ES002109]
- Swiss National Science Foundation [P2ELP2_178238]
- Ludwig Center fellowship
- NIH Molecular Biophysics Training Grant [NIH/NIGMS T32 GM008313]
- National Science Foundation Graduate Research Fellowship
- Johnson Johnson
- Swiss National Science Foundation (SNF) [P2ELP2_178238] Funding Source: Swiss National Science Foundation (SNF)
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This study proposes the use of ionic liquids as a skin transport facilitator to deliver thrombin-sensitive nanosensors for prolonged monitoring of pulmonary embolism. The results demonstrate significant transdermal diffusion of the nanosensors using co-formulation with choline and geranic acid ionic liquids, providing sustained release into the blood for 72 hours. The nanosensors release reporter molecules into the urine in response to activation of the clotting cascade and retain diagnostic power for 24 hours in an acute pulmonary embolism mouse model.
Blood clotting disorders such as pulmonary embolism are associated with high morbidity and mortality. A large portion of thrombotic events occur postoperative and after hospital discharge. Therefore, easily applicable, noninvasive, and long-term monitoring of thrombosis occurrence is critical for urgent clinical intervention. Here, the use is proposed of ionic liquids as a skin transport facilitator to deliver thrombin-sensitive nanosensors that enable prolonged monitoring of pulmonary embolism. Co-formulation of nanosensors with choline and geranic acid (CAGE) ionic liquids demonstrates significant transdermal diffusion into the dermis of the skin and provides sustained release into the blood throughout 72 h. Upon reaching the systemic circulation, the nanosensors release reporter molecules into the urine by responding to activation of the clotting cascade and retain a diagnostic power for 24 h in an acute pulmonary embolism mouse model. These results demonstrate a proof-of-concept disease monitoring system that can be topically applied by patients and potentially reduce mortality and high cost of hospitalization.
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