Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury
Abstract Acute myocardial infarction (AMI) is usually caused by coronary thrombosis. However, the short half-life, lack of targetability and inevitable ischemia/reperfusion injury secondary to revascularization, which characterizes tissue plasminogen activator (tPA) limit its thrombolytic efficacy f...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01686-1 |
| _version_ | 1811291922710396928 |
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| author | Xiaoyu Guo Ting Hong Jie Zang Rongjiao Shao Xumin Hou Kai Wang Weizhuo Liu Fan Su Bin He |
| author_facet | Xiaoyu Guo Ting Hong Jie Zang Rongjiao Shao Xumin Hou Kai Wang Weizhuo Liu Fan Su Bin He |
| author_sort | Xiaoyu Guo |
| collection | DOAJ |
| description | Abstract Acute myocardial infarction (AMI) is usually caused by coronary thrombosis. However, the short half-life, lack of targetability and inevitable ischemia/reperfusion injury secondary to revascularization, which characterizes tissue plasminogen activator (tPA) limit its thrombolytic efficacy for AMI. To address the targeted and site-specific delivery of tPA, the current study reports the construction of a thrombus-targeting and responsive biomimetic nanoparticle (PTPN) for spatiotemporal treatment of AMI. PTPN was constituted by the thrombus microenvironment- responsive phenylboronic acid (PBA) nanocarrier, antioxidant molecular protocatechualdehyde (PC) and tPA with thrombolytic effect, which were enclosed by the platelet membrane. The thrombus-targeting capability of the platelet membrane enabled the adhesion of PTPN to damaged endothelial cells. The nanoparticle disintegrated under slightly acid condition and re-opened the infarct-related artery during the period of ischemia. Sequentially, ROS induced by blood reperfusion was eliminated by PC released from particle disintegration, and the cardiomyocyte mitochondrial function was protected from reperfusion injury. Therefore, this thrombus-specific/responsive biomimetic nanomedicine provides a spatiotemporal paradigm for AMI treatment with promising clinical translation prospects. |
| first_indexed | 2024-04-13T04:37:35Z |
| format | Article |
| id | doaj.art-23cd9fcd2eb44001a7286e295b6f5a9f |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-13T04:37:35Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-23cd9fcd2eb44001a7286e295b6f5a9f2022-12-22T03:02:07ZengBMCJournal of Nanobiotechnology1477-31552022-12-0120111810.1186/s12951-022-01686-1Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injuryXiaoyu Guo0Ting Hong1Jie Zang2Rongjiao Shao3Xumin Hou4Kai Wang5Weizhuo Liu6Fan Su7Bin He8Department of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineThe Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji UniversityDepartment of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineCentral Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of MedicineAbstract Acute myocardial infarction (AMI) is usually caused by coronary thrombosis. However, the short half-life, lack of targetability and inevitable ischemia/reperfusion injury secondary to revascularization, which characterizes tissue plasminogen activator (tPA) limit its thrombolytic efficacy for AMI. To address the targeted and site-specific delivery of tPA, the current study reports the construction of a thrombus-targeting and responsive biomimetic nanoparticle (PTPN) for spatiotemporal treatment of AMI. PTPN was constituted by the thrombus microenvironment- responsive phenylboronic acid (PBA) nanocarrier, antioxidant molecular protocatechualdehyde (PC) and tPA with thrombolytic effect, which were enclosed by the platelet membrane. The thrombus-targeting capability of the platelet membrane enabled the adhesion of PTPN to damaged endothelial cells. The nanoparticle disintegrated under slightly acid condition and re-opened the infarct-related artery during the period of ischemia. Sequentially, ROS induced by blood reperfusion was eliminated by PC released from particle disintegration, and the cardiomyocyte mitochondrial function was protected from reperfusion injury. Therefore, this thrombus-specific/responsive biomimetic nanomedicine provides a spatiotemporal paradigm for AMI treatment with promising clinical translation prospects.https://doi.org/10.1186/s12951-022-01686-1Myocardial infarctionIschemia/reperfusion injuryMitochondrial protectionpH responsive nanomedicinePlatelet biomimetics |
| spellingShingle | Xiaoyu Guo Ting Hong Jie Zang Rongjiao Shao Xumin Hou Kai Wang Weizhuo Liu Fan Su Bin He Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury Journal of Nanobiotechnology Myocardial infarction Ischemia/reperfusion injury Mitochondrial protection pH responsive nanomedicine Platelet biomimetics |
| title | Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury |
| title_full | Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury |
| title_fullStr | Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury |
| title_full_unstemmed | Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury |
| title_short | Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury |
| title_sort | thrombus specific responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia reperfusion injury |
| topic | Myocardial infarction Ischemia/reperfusion injury Mitochondrial protection pH responsive nanomedicine Platelet biomimetics |
| url | https://doi.org/10.1186/s12951-022-01686-1 |
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