Flow rate modulates focused ultrasound-mediated vascular delivery of microRNA
Gene therapy targeting ischemic heart disease is a promising therapeutic avenue, but it is mostly restricted to viral-based delivery approaches which are limited due to off-target immunological responses. Focused ultrasound presents a non-viral, image-guided technique in which circulating intravascu...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253124003135 |
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| author | Stephanie He Davindra Singh Brandon Helfield |
| author_facet | Stephanie He Davindra Singh Brandon Helfield |
| author_sort | Stephanie He |
| collection | DOAJ |
| description | Gene therapy targeting ischemic heart disease is a promising therapeutic avenue, but it is mostly restricted to viral-based delivery approaches which are limited due to off-target immunological responses. Focused ultrasound presents a non-viral, image-guided technique in which circulating intravascular microbubble contrast agents can reversibly enhance vascular permeability and gene penetration. Here, we explore the influence of flow rate on the microbubble-assisted delivery of miR-126, a potent pro-angiogenic biologic, using a custom acoustically coupled pressurized mesenteric artery model. We demonstrate that under the same ultrasound conditions, increased flow rates enhance microbubble-mediated cell permeability; yet, miR-126 delivery itself exhibits a negative correlation with increasing flow velocity. Post-ultrasound assays confirmed vessel vasoreactivity, maintaining vasoconstriction and vasodilation capacities. These findings underscore the critical role microbubble flow rate plays in focused ultrasound gene therapy, especially notable for applications in which blood velocity itself is a salient pathophysiological indicator of disease progression, including ischemia. |
| format | Article |
| id | doaj-art-b196f305407a4b9fa0ace80175f2c786 |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-b196f305407a4b9fa0ace80175f2c7862025-01-03T04:08:38ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102426Flow rate modulates focused ultrasound-mediated vascular delivery of microRNAStephanie He0Davindra Singh1Brandon Helfield2Department of Biology, Concordia University, Montreal, QC H4B 1R6, CanadaDepartment of Biology, Concordia University, Montreal, QC H4B 1R6, CanadaDepartment of Biology, Concordia University, Montreal, QC H4B 1R6, Canada; Department of Physics, Concordia University, Montreal, QC H4B 1R6, Canada; Corresponding author: Brandon Helfield, Department of Biology, Concordia University, Montreal, QC H4B 1R6, CanadaGene therapy targeting ischemic heart disease is a promising therapeutic avenue, but it is mostly restricted to viral-based delivery approaches which are limited due to off-target immunological responses. Focused ultrasound presents a non-viral, image-guided technique in which circulating intravascular microbubble contrast agents can reversibly enhance vascular permeability and gene penetration. Here, we explore the influence of flow rate on the microbubble-assisted delivery of miR-126, a potent pro-angiogenic biologic, using a custom acoustically coupled pressurized mesenteric artery model. We demonstrate that under the same ultrasound conditions, increased flow rates enhance microbubble-mediated cell permeability; yet, miR-126 delivery itself exhibits a negative correlation with increasing flow velocity. Post-ultrasound assays confirmed vessel vasoreactivity, maintaining vasoconstriction and vasodilation capacities. These findings underscore the critical role microbubble flow rate plays in focused ultrasound gene therapy, especially notable for applications in which blood velocity itself is a salient pathophysiological indicator of disease progression, including ischemia.http://www.sciencedirect.com/science/article/pii/S2162253124003135MT: Delivery Strategiesfocused ultrasoundgene deliverymyographdrug deliveryacoustic cavitation |
| spellingShingle | Stephanie He Davindra Singh Brandon Helfield Flow rate modulates focused ultrasound-mediated vascular delivery of microRNA Molecular Therapy: Nucleic Acids MT: Delivery Strategies focused ultrasound gene delivery myograph drug delivery acoustic cavitation |
| title | Flow rate modulates focused ultrasound-mediated vascular delivery of microRNA |
| title_full | Flow rate modulates focused ultrasound-mediated vascular delivery of microRNA |
| title_fullStr | Flow rate modulates focused ultrasound-mediated vascular delivery of microRNA |
| title_full_unstemmed | Flow rate modulates focused ultrasound-mediated vascular delivery of microRNA |
| title_short | Flow rate modulates focused ultrasound-mediated vascular delivery of microRNA |
| title_sort | flow rate modulates focused ultrasound mediated vascular delivery of microrna |
| topic | MT: Delivery Strategies focused ultrasound gene delivery myograph drug delivery acoustic cavitation |
| url | http://www.sciencedirect.com/science/article/pii/S2162253124003135 |
| work_keys_str_mv | AT stephaniehe flowratemodulatesfocusedultrasoundmediatedvasculardeliveryofmicrorna AT davindrasingh flowratemodulatesfocusedultrasoundmediatedvasculardeliveryofmicrorna AT brandonhelfield flowratemodulatesfocusedultrasoundmediatedvasculardeliveryofmicrorna |