β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome model
Anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic vascular occlusion and maternal morbidity. Anti-coagulants remain pivotal drugs for the management of APS, but a significant proportion of patients do not benefit from long-term anti-coagulation and may req...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1520619/full |
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| author | Paolo Durigutto Maria Cristina Grimaldi Sara Bozzer Elena Raschi Pierluigi Meroni Francesco Tedesco Paolo Macor |
| author_facet | Paolo Durigutto Maria Cristina Grimaldi Sara Bozzer Elena Raschi Pierluigi Meroni Francesco Tedesco Paolo Macor |
| author_sort | Paolo Durigutto |
| collection | DOAJ |
| description | Anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic vascular occlusion and maternal morbidity. Anti-coagulants remain pivotal drugs for the management of APS, but a significant proportion of patients do not benefit from long-term anti-coagulation and may require an alternative therapy to prevent antibody deposition and vascular thrombosis. We have developed a therapeutic approach based on the use of safe polymeric nanoparticles that selectively target beta2-glycoprotein I (β2GPI) deposited on endothelial cells (tNPs). Their efficacy was tested in a rat model of APS developed by infusing patients’ sera containing medium–high titer antibodies against domain I of β2GPI. The tNPs bearing a CH2-deleted anti-β2GPI recombinant antibody as a targeting agent recognize β2GPI deposited on endothelial cells but failed to induce blood clot formation. The tNPs infused into rats immediately before APS sera competed with patients’ antibodies, preventing their binding to deposited β2GPI and, as a consequence, resulted in thrombus formations and occlusion of mesenteric vessels. Similar results were obtained by injecting tNPs 24 hours before the administration of patients’ sera to induce blood clot formation. Our findings suggest that β2GPI-targeted polymeric nanoparticles represent a stable and safe approach to prevent thrombus formation and vessel occlusion in a rat model of APS and may be used to control thrombosis developing in APS patients as a result of acute triggering events. |
| format | Article |
| id | doaj-art-e8ca4311d8c14984995b90215e241ee9 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-e8ca4311d8c14984995b90215e241ee92025-08-20T02:45:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15206191520619β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome modelPaolo Durigutto0Maria Cristina Grimaldi1Sara Bozzer2Elena Raschi3Pierluigi Meroni4Francesco Tedesco5Paolo Macor6Laboratory of Immuno-Rheumatology Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyLaboratory of Immuno-Rheumatology Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, ItalyLaboratory of Immuno-Rheumatology Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, ItalyLaboratory of Immuno-Rheumatology Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, ItalyDepartment of Life Sciences, University of Trieste, Trieste, ItalyAnti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic vascular occlusion and maternal morbidity. Anti-coagulants remain pivotal drugs for the management of APS, but a significant proportion of patients do not benefit from long-term anti-coagulation and may require an alternative therapy to prevent antibody deposition and vascular thrombosis. We have developed a therapeutic approach based on the use of safe polymeric nanoparticles that selectively target beta2-glycoprotein I (β2GPI) deposited on endothelial cells (tNPs). Their efficacy was tested in a rat model of APS developed by infusing patients’ sera containing medium–high titer antibodies against domain I of β2GPI. The tNPs bearing a CH2-deleted anti-β2GPI recombinant antibody as a targeting agent recognize β2GPI deposited on endothelial cells but failed to induce blood clot formation. The tNPs infused into rats immediately before APS sera competed with patients’ antibodies, preventing their binding to deposited β2GPI and, as a consequence, resulted in thrombus formations and occlusion of mesenteric vessels. Similar results were obtained by injecting tNPs 24 hours before the administration of patients’ sera to induce blood clot formation. Our findings suggest that β2GPI-targeted polymeric nanoparticles represent a stable and safe approach to prevent thrombus formation and vessel occlusion in a rat model of APS and may be used to control thrombosis developing in APS patients as a result of acute triggering events.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1520619/fullnanoparticlesthrombosisanti-phospholipid syndromeβ2GPIrat model |
| spellingShingle | Paolo Durigutto Maria Cristina Grimaldi Sara Bozzer Elena Raschi Pierluigi Meroni Francesco Tedesco Paolo Macor β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome model Frontiers in Immunology nanoparticles thrombosis anti-phospholipid syndrome β2GPI rat model |
| title | β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome model |
| title_full | β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome model |
| title_fullStr | β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome model |
| title_full_unstemmed | β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome model |
| title_short | β2GPI-targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti-phospholipid syndrome model |
| title_sort | β2gpi targeted polymeric nanoparticles form a protective layer to prevent vascular thrombosis in an anti phospholipid syndrome model |
| topic | nanoparticles thrombosis anti-phospholipid syndrome β2GPI rat model |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1520619/full |
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