Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertension
Backgroud:In-situ thrombosis is a significant pathophysiological basis for the development of pulmonary hypertension (PH). However, thrombolytic therapy for in-situ thrombus in PH was often hampered by the apparent side effects and the low bioavailability of common thrombolytic medications. Nanoscal...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2022.1038829/full |
| _version_ | 1811182451429474304 |
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| author | Jingtao Li Xiaofeng Zhang Yingying Mo Tongtong Huang Huaqing Rao Zhenyuan Tan Liuliu Huang Decai Zeng Chunlan Jiang Yanfen Zhong Yongzhi Cai Binbin Liang Ji Wu |
| author_facet | Jingtao Li Xiaofeng Zhang Yingying Mo Tongtong Huang Huaqing Rao Zhenyuan Tan Liuliu Huang Decai Zeng Chunlan Jiang Yanfen Zhong Yongzhi Cai Binbin Liang Ji Wu |
| author_sort | Jingtao Li |
| collection | DOAJ |
| description | Backgroud:In-situ thrombosis is a significant pathophysiological basis for the development of pulmonary hypertension (PH). However, thrombolytic therapy for in-situ thrombus in PH was often hampered by the apparent side effects and the low bioavailability of common thrombolytic medications. Nanoscale cyclic RGD (cRGD)-decorated liposomes have received much attention thanks to their thrombus-targeting and biodegradability properties. As a result, we synthesized urokinase-loaded cRGD-decorated liposome (UK-cRGD-Liposome) for therapy of in-situ thrombosis as an exploration of pulmonary hypertensive novel therapeutic approaches.Purpose: To evaluate the utilize of UK-cRGD-Liposome for targeted thrombolysis of in-situ thrombus in PH and to explore the potential mechanisms of in-situ thrombus involved in the development of PH.Methods: UK-cRGD-Liposome nanoscale drug delivery system was prepared using combined methods of thin-film hydration and sonication. Induced PH via subcutaneous injection of monocrotaline (MCT). Fibrin staining (modified MSB method) was applied to detect the number of vessels within-situ thrombi in PH. Echocardiography, hematoxylin-eosin (H & E) staining, and Masson’s trichrome staining were used to analyze right ventricular (RV) function, pulmonary vascular remodeling, as well as RV remodeling.Results: The number of vessels with in-situ thrombi revealed that UK-cRGD-Liposome could actively target urokinase to in-situ thrombi and release its payload in a controlled manner in the in vivo environment, thereby enhancing the thrombolytic effect of urokinase. Pulmonary artery hemodynamics and echocardiography indicated a dramatical decrease in pulmonary artery pressure and a significant improvement in RV function post targeted thrombolytic therapy. Moreover, pulmonary vascular remodeling and RV remodeling were significantly restricted post targeted thrombolytic therapy.Conclusion: UK-cRGD-Liposome can restrict the progression of PH and improve RV function by targeting the dissolution of pulmonary hypertensive in-situ thrombi, which may provide promising therapeutic approaches for PH. |
| first_indexed | 2024-04-11T09:32:35Z |
| format | Article |
| id | doaj.art-b58f1ff5ceef41859efa2d25e8b27ba9 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-11T09:32:35Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-b58f1ff5ceef41859efa2d25e8b27ba92022-12-22T04:31:50ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-10-011010.3389/fbioe.2022.10388291038829Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertensionJingtao Li0Xiaofeng Zhang1Yingying Mo2Tongtong Huang3Huaqing Rao4Zhenyuan Tan5Liuliu Huang6Decai Zeng7Chunlan Jiang8Yanfen Zhong9Yongzhi Cai10Binbin Liang11Ji Wu12Department of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaPharmaceutical College, Guangxi Medical University, Nanning, ChinaDepartment of Cardiothoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, ChinaBackgroud:In-situ thrombosis is a significant pathophysiological basis for the development of pulmonary hypertension (PH). However, thrombolytic therapy for in-situ thrombus in PH was often hampered by the apparent side effects and the low bioavailability of common thrombolytic medications. Nanoscale cyclic RGD (cRGD)-decorated liposomes have received much attention thanks to their thrombus-targeting and biodegradability properties. As a result, we synthesized urokinase-loaded cRGD-decorated liposome (UK-cRGD-Liposome) for therapy of in-situ thrombosis as an exploration of pulmonary hypertensive novel therapeutic approaches.Purpose: To evaluate the utilize of UK-cRGD-Liposome for targeted thrombolysis of in-situ thrombus in PH and to explore the potential mechanisms of in-situ thrombus involved in the development of PH.Methods: UK-cRGD-Liposome nanoscale drug delivery system was prepared using combined methods of thin-film hydration and sonication. Induced PH via subcutaneous injection of monocrotaline (MCT). Fibrin staining (modified MSB method) was applied to detect the number of vessels within-situ thrombi in PH. Echocardiography, hematoxylin-eosin (H & E) staining, and Masson’s trichrome staining were used to analyze right ventricular (RV) function, pulmonary vascular remodeling, as well as RV remodeling.Results: The number of vessels with in-situ thrombi revealed that UK-cRGD-Liposome could actively target urokinase to in-situ thrombi and release its payload in a controlled manner in the in vivo environment, thereby enhancing the thrombolytic effect of urokinase. Pulmonary artery hemodynamics and echocardiography indicated a dramatical decrease in pulmonary artery pressure and a significant improvement in RV function post targeted thrombolytic therapy. Moreover, pulmonary vascular remodeling and RV remodeling were significantly restricted post targeted thrombolytic therapy.Conclusion: UK-cRGD-Liposome can restrict the progression of PH and improve RV function by targeting the dissolution of pulmonary hypertensive in-situ thrombi, which may provide promising therapeutic approaches for PH.https://www.frontiersin.org/articles/10.3389/fbioe.2022.1038829/fullcyclic RGD peptideliposomein-situ thrombustargeted thrombolysispulmonary hypertensionright ventricular function |
| spellingShingle | Jingtao Li Xiaofeng Zhang Yingying Mo Tongtong Huang Huaqing Rao Zhenyuan Tan Liuliu Huang Decai Zeng Chunlan Jiang Yanfen Zhong Yongzhi Cai Binbin Liang Ji Wu Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertension Frontiers in Bioengineering and Biotechnology cyclic RGD peptide liposome in-situ thrombus targeted thrombolysis pulmonary hypertension right ventricular function |
| title | Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertension |
| title_full | Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertension |
| title_fullStr | Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertension |
| title_full_unstemmed | Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertension |
| title_short | Urokinase-loaded cyclic RGD-decorated liposome targeted therapy for in-situ thrombus of pulmonary arteriole of pulmonary hypertension |
| title_sort | urokinase loaded cyclic rgd decorated liposome targeted therapy for in situ thrombus of pulmonary arteriole of pulmonary hypertension |
| topic | cyclic RGD peptide liposome in-situ thrombus targeted thrombolysis pulmonary hypertension right ventricular function |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2022.1038829/full |
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