Poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps">d</span></i>, <i><span style="font-variant: small-caps">l</span></i>-Aspartyl-Arg-Gly-Asp-Ser-Based Urokinase Nanoparticles for Thrombolysis Therapy
The most concerning adverse effects of thrombolytic agents are major bleeding and intracranial hemorrhage due to their short half-life, low fibrin specificity, and high dosage. To alleviate bleeding side effects during thrombolytic therapy which would bring about the risk of aggravation, we try to f...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/6/2578 |
| _version_ | 1827748413239721984 |
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| author | Shuangling Chen Meng Liang Chengli Wu Xiaoyi Zhang Yuji Wang Ming Zhao |
| author_facet | Shuangling Chen Meng Liang Chengli Wu Xiaoyi Zhang Yuji Wang Ming Zhao |
| author_sort | Shuangling Chen |
| collection | DOAJ |
| description | The most concerning adverse effects of thrombolytic agents are major bleeding and intracranial hemorrhage due to their short half-life, low fibrin specificity, and high dosage. To alleviate bleeding side effects during thrombolytic therapy which would bring about the risk of aggravation, we try to find a novel biodegradable delivery nanosystem to carry drugs to target the thrombus, reduce the dosage of the drug, and system side effects. A novel urokinase/poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps;">d</span></i>, <i><span style="font-variant: small-caps;">l</span></i>-aspartyl-Arg-Gly-Asp-Ser complex (UK/PD-RGDS) was synthesized and simply prepared. Its thrombolytic potency was assayed by the bubble-rising method and in vitro thrombolytic activity by the thrombus clot lysis assay separately. The in vivo thrombolytic activity and bleeding complication were evaluated by a rat model of carotid arteriovenous bypass thrombolysis. The thrombolytic potency (1288.19 ± 155.20 U/mg) of the UK/PD-RGDS complex nano-globule (18–130 nm) was 1.3 times that of commercial UK (966.77 ± 148.08 U/mg). In vivo, the UK/PD-RGDS complex (2000 IU/kg) could reduce the dose of UK by 90% while achieving the equivalent thrombolysis effect as the free UK (20,000 IU/kg). Additionally, the UK/PD-RGDS complex decreased the tail bleeding time compared with UK. The organ distribution of the FITC-UK/PD-RGDS complex was explored in the rat model. The UK/PD-RGDS complex could provide a promising platform to enhance thrombolytic efficacy significantly and reduce the major bleeding degree. |
| first_indexed | 2024-03-11T06:07:51Z |
| format | Article |
| id | doaj.art-ddda3c8a2e314bb6a78f45d47b834061 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T06:07:51Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ddda3c8a2e314bb6a78f45d47b8340612023-11-17T12:52:19ZengMDPI AGMolecules1420-30492023-03-01286257810.3390/molecules28062578Poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps">d</span></i>, <i><span style="font-variant: small-caps">l</span></i>-Aspartyl-Arg-Gly-Asp-Ser-Based Urokinase Nanoparticles for Thrombolysis TherapyShuangling Chen0Meng Liang1Chengli Wu2Xiaoyi Zhang3Yuji Wang4Ming Zhao5School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, ChinaSchool of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, ChinaSchool of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, ChinaSchool of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, ChinaSchool of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, ChinaSchool of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, ChinaThe most concerning adverse effects of thrombolytic agents are major bleeding and intracranial hemorrhage due to their short half-life, low fibrin specificity, and high dosage. To alleviate bleeding side effects during thrombolytic therapy which would bring about the risk of aggravation, we try to find a novel biodegradable delivery nanosystem to carry drugs to target the thrombus, reduce the dosage of the drug, and system side effects. A novel urokinase/poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps;">d</span></i>, <i><span style="font-variant: small-caps;">l</span></i>-aspartyl-Arg-Gly-Asp-Ser complex (UK/PD-RGDS) was synthesized and simply prepared. Its thrombolytic potency was assayed by the bubble-rising method and in vitro thrombolytic activity by the thrombus clot lysis assay separately. The in vivo thrombolytic activity and bleeding complication were evaluated by a rat model of carotid arteriovenous bypass thrombolysis. The thrombolytic potency (1288.19 ± 155.20 U/mg) of the UK/PD-RGDS complex nano-globule (18–130 nm) was 1.3 times that of commercial UK (966.77 ± 148.08 U/mg). In vivo, the UK/PD-RGDS complex (2000 IU/kg) could reduce the dose of UK by 90% while achieving the equivalent thrombolysis effect as the free UK (20,000 IU/kg). Additionally, the UK/PD-RGDS complex decreased the tail bleeding time compared with UK. The organ distribution of the FITC-UK/PD-RGDS complex was explored in the rat model. The UK/PD-RGDS complex could provide a promising platform to enhance thrombolytic efficacy significantly and reduce the major bleeding degree.https://www.mdpi.com/1420-3049/28/6/2578urokinasethrombolytictargetednano delivery systemRGDS |
| spellingShingle | Shuangling Chen Meng Liang Chengli Wu Xiaoyi Zhang Yuji Wang Ming Zhao Poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps">d</span></i>, <i><span style="font-variant: small-caps">l</span></i>-Aspartyl-Arg-Gly-Asp-Ser-Based Urokinase Nanoparticles for Thrombolysis Therapy Molecules urokinase thrombolytic targeted nano delivery system RGDS |
| title | Poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps">d</span></i>, <i><span style="font-variant: small-caps">l</span></i>-Aspartyl-Arg-Gly-Asp-Ser-Based Urokinase Nanoparticles for Thrombolysis Therapy |
| title_full | Poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps">d</span></i>, <i><span style="font-variant: small-caps">l</span></i>-Aspartyl-Arg-Gly-Asp-Ser-Based Urokinase Nanoparticles for Thrombolysis Therapy |
| title_fullStr | Poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps">d</span></i>, <i><span style="font-variant: small-caps">l</span></i>-Aspartyl-Arg-Gly-Asp-Ser-Based Urokinase Nanoparticles for Thrombolysis Therapy |
| title_full_unstemmed | Poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps">d</span></i>, <i><span style="font-variant: small-caps">l</span></i>-Aspartyl-Arg-Gly-Asp-Ser-Based Urokinase Nanoparticles for Thrombolysis Therapy |
| title_short | Poly-<i>α</i>, <i>β</i>-<i><span style="font-variant: small-caps">d</span></i>, <i><span style="font-variant: small-caps">l</span></i>-Aspartyl-Arg-Gly-Asp-Ser-Based Urokinase Nanoparticles for Thrombolysis Therapy |
| title_sort | poly i α i i β i i span style font variant small caps d span i i span style font variant small caps l span i aspartyl arg gly asp ser based urokinase nanoparticles for thrombolysis therapy |
| topic | urokinase thrombolytic targeted nano delivery system RGDS |
| url | https://www.mdpi.com/1420-3049/28/6/2578 |
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