Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic Therapy

Owing to the short half‐life, restricted targeting capability, and high bleeding risk associated with thrombolytic drugs, safe and effective thrombolytic therapy remains challenging. Based on the natural targeting and immune escape functions of platelets during thrombosis, spatiotemporally controlle...

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Main Authors: Wenli Zhang, Maoyuan Sun, Lian Xu, Sijin Chen, Xiyue Rong, Junrui Wang, Jia Liu, Bo Liu, Jie Xu, Ying Luo, Qianying Du, Yi Wang, Yun Liu, Zhigang Wang, Haitao Ran, Dajing Guo
Format: Article
Language:English
Published: Wiley-VCH 2025-06-01
Series:Small Structures
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Online Access:https://doi.org/10.1002/sstr.202400541
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author Wenli Zhang
Maoyuan Sun
Lian Xu
Sijin Chen
Xiyue Rong
Junrui Wang
Jia Liu
Bo Liu
Jie Xu
Ying Luo
Qianying Du
Yi Wang
Yun Liu
Zhigang Wang
Haitao Ran
Dajing Guo
author_facet Wenli Zhang
Maoyuan Sun
Lian Xu
Sijin Chen
Xiyue Rong
Junrui Wang
Jia Liu
Bo Liu
Jie Xu
Ying Luo
Qianying Du
Yi Wang
Yun Liu
Zhigang Wang
Haitao Ran
Dajing Guo
author_sort Wenli Zhang
collection DOAJ
description Owing to the short half‐life, restricted targeting capability, and high bleeding risk associated with thrombolytic drugs, safe and effective thrombolytic therapy remains challenging. Based on the natural targeting and immune escape functions of platelets during thrombosis, spatiotemporally controlled nanobubbles (PAF@M) are developed to specifically target thrombus sites. These nanobubbles are designed by loading an air core of perfluoropentane (PFP) and l‐arginine within a poly(lactic‐co‐glycolic acid) shell and coating it with a platelet membrane. Under stimulation with low‐intensity focused ultrasound (LIFU), physical shear stress promotes deep penetration of the nanobubbles into the thrombus. Moreover, the liquid–gas phase transition of PFP and the release of nitric oxide synergistically enhance ultrasonic cavitation to disrupt the thrombus structure. In terms of mechanism, these gas molecules induce acoustic pore action to disrupt the fibrin network structure, loosening the interior of the thrombus, and act specifically on the surfaces of red blood cells and activated platelets, launching a comprehensive attack on the thrombus. It is believed that PAF@M nanobubbles will delay the progression of thrombosis and achieve safe and highly effective thrombolytic therapy. This simple LIFU response principle has the potential to be a safer and more effective alternative to current pharmaceutical approaches.
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issn 2688-4062
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publishDate 2025-06-01
publisher Wiley-VCH
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series Small Structures
spelling doaj-art-e4a1ec46435f4f018cfe22157fd38edd2025-08-20T02:02:58ZengWiley-VCHSmall Structures2688-40622025-06-0166n/an/a10.1002/sstr.202400541Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic TherapyWenli Zhang0Maoyuan Sun1Lian Xu2Sijin Chen3Xiyue Rong4Junrui Wang5Jia Liu6Bo Liu7Jie Xu8Ying Luo9Qianying Du10Yi Wang11Yun Liu12Zhigang Wang13Haitao Ran14Dajing Guo15Department of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Neurosurgery Huashan Hospital Fudan University Shanghai 200000 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Ultrasound & Chongqing Key Laboratory of Ultrasound Molecular Imaging The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Ultrasound & Chongqing Key Laboratory of Ultrasound Molecular Imaging The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaDepartment of Radiology The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 ChinaOwing to the short half‐life, restricted targeting capability, and high bleeding risk associated with thrombolytic drugs, safe and effective thrombolytic therapy remains challenging. Based on the natural targeting and immune escape functions of platelets during thrombosis, spatiotemporally controlled nanobubbles (PAF@M) are developed to specifically target thrombus sites. These nanobubbles are designed by loading an air core of perfluoropentane (PFP) and l‐arginine within a poly(lactic‐co‐glycolic acid) shell and coating it with a platelet membrane. Under stimulation with low‐intensity focused ultrasound (LIFU), physical shear stress promotes deep penetration of the nanobubbles into the thrombus. Moreover, the liquid–gas phase transition of PFP and the release of nitric oxide synergistically enhance ultrasonic cavitation to disrupt the thrombus structure. In terms of mechanism, these gas molecules induce acoustic pore action to disrupt the fibrin network structure, loosening the interior of the thrombus, and act specifically on the surfaces of red blood cells and activated platelets, launching a comprehensive attack on the thrombus. It is believed that PAF@M nanobubbles will delay the progression of thrombosis and achieve safe and highly effective thrombolytic therapy. This simple LIFU response principle has the potential to be a safer and more effective alternative to current pharmaceutical approaches.https://doi.org/10.1002/sstr.202400541low‐intensity focused ultrasoundpenetrationphase transitiontargetingthrombolytic therapy
spellingShingle Wenli Zhang
Maoyuan Sun
Lian Xu
Sijin Chen
Xiyue Rong
Junrui Wang
Jia Liu
Bo Liu
Jie Xu
Ying Luo
Qianying Du
Yi Wang
Yun Liu
Zhigang Wang
Haitao Ran
Dajing Guo
Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic Therapy
Small Structures
low‐intensity focused ultrasound
penetration
phase transition
targeting
thrombolytic therapy
title Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic Therapy
title_full Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic Therapy
title_fullStr Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic Therapy
title_full_unstemmed Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic Therapy
title_short Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic Therapy
title_sort low intensity focused ultrasound responsive nanobubbles enhance thrombus targeting and penetration for highly effective thrombolytic therapy
topic low‐intensity focused ultrasound
penetration
phase transition
targeting
thrombolytic therapy
url https://doi.org/10.1002/sstr.202400541
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