Academic Journal
Enzyme-coupled polymersome microreactor for point-of-care blood urea sensing.
| Τίτλος: | Enzyme-coupled polymersome microreactor for point-of-care blood urea sensing. |
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| Συγγραφείς: | Belin C; Faculté de Pharmacie, Université de Montréal, Montreal, Quebec H3T 1J4, Canada; CPE Lyon, Villeurbanne 69100, Auvergne-Rhône-Alpes, France., Lenglet E; Faculté de Pharmacie, Université de Montréal, Montreal, Quebec H3T 1J4, Canada; CPE Lyon, Villeurbanne 69100, Auvergne-Rhône-Alpes, France., Al-Hawat ML; Faculté de Pharmacie, Université de Montréal, Montreal, Quebec H3T 1J4, Canada., Caron J; Faculté de Pharmacie, Université de Montréal, Montreal, Quebec H3T 1J4, Canada., Bartumeu EG; Faculté de Pharmacie, Université de Montréal, Montreal, Quebec H3T 1J4, Canada; Faculté Sciences et Ingénierie, Université de Toulouse, Toulouse 31062, Occitanie, France., Djebbar S; Faculté de Pharmacie, Université de Montréal, Montreal, Quebec H3T 1J4, Canada., Matoori S; Faculté de Pharmacie, Université de Montréal, Montreal, Quebec H3T 1J4, Canada. Electronic address: simon.matoori@umontreal.ca. |
| Πηγή: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2026 Feb 10; Vol. 390, pp. 114557. Date of Electronic Publication: 2025 Dec 18. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam : Elsevier Science Publishers, 1984- |
| Ιατρικοί όροι (MeSH): | Urea*/blood , Urease*/chemistry , Urease*/metabolism , Polyethylene Glycols*/chemistry , Polystyrenes*/chemistry , Point-of-Care Systems*, Ammonia/analysis ; Ammonia/blood ; Animals ; Humans ; Hydrogen-Ion Concentration ; Mice |
| Περίληψη: | Vesicular microreactors have gained broad interest in drug delivery, biodetoxification, and green chemistry. We have expanded their use to diagnostic applications by leveraging the selective permeability of the vesicular membrane. In the past, we developed a transmembrane pH-gradient polymeric microreactor to sense ammonia, a widely used biomarker in liver disease. After diffusing across the membrane, ammonia is protonated in the acidic lumen of the polymersome. The pH increase is detected by a pH-sensitive near-infrared fluorophore in the lumen. The high ammonia selectivity of this polymersome microreactor relies on the highly hydrophobic membrane of poly(styrene)-b-poly(ethylene glycol) polymersomes. In this study, we are combining ammonia-sensing polymersomes with a highly selective ammonia-generating enzyme, urease, to expand the analyte space and enable urea sensing in whole blood. Blood urea is a widely used biomarker in kidney disease, notably to determine the adequate duration of hemodialysis. In clinical routine, blood urea measurements are performed in centralized laboratories. A bedside test would enable real-time urea monitoring during hemodialysis with the potential to reduce the risk of over- and underdialysis. We first optimized the assay components and parameters (PS-b-PEG polymersomes, pH-sensitive dye, urease, incubation time and temperature) to optimize the sensor response and kinetics in phosphate buffer at pH 7.4. The urease-coupled polymersome assay was subsequently tested in urea-spiked fresh mouse blood. We observed a rapid and linear response at clinically relevant urea concentrations. Based on these results, the assay was tested in an IRB-approved study in healthy volunteers. In fresh capillary blood, the assay was able to discriminate three clinically relevant spiked urea concentrations in under one minute. Therefore, coupling the urease-catalyzed hydrolysis of urea with ammonia-sensing polymersomes yielded a blood urea assay with high selectivity and a rapid response at clinically relevant concentrations. These results highlight the potential of combining a highly selective ammonia-generating enzyme with ammonia-sensing polymersome microreactors for blood metabolite sensing at the point-of-care. (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare the following competing financial interest(s): SM is a co-inventor of two patents on ammonia-sequestering and ammonia-sensing poly(styrene)-b-poly(ethylene glycol) polymersomes. |
| Contributed Indexing: | Keywords: Analyte sensing; Enzyme; Near-infrared fluorescence; Poly(styrene)-b-poly(ethylene glycol); Polymersomes; Urease |
| Substance Nomenclature: | 8W8T17847W (Urea) EC 3.5.1.5 (Urease) 3WJQ0SDW1A (Polyethylene Glycols) 7664-41-7 (Ammonia) 0 (Polystyrenes) |
| Entry Date(s): | Date Created: 20251220 Date Completed: 20260119 Latest Revision: 20260705 |
| Update Code: | 20260705 |
| DOI: | 10.1016/j.jconrel.2025.114557 |
| PMID: | 41421743 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-4995 |
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| DOI: | 10.1016/j.jconrel.2025.114557 |