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Acta Biomaterialia: structure-property-function relationships in biomaterials v.70, 2018년, pp.227 - 236   SCI SCIE SCOPUS
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Cyclic RGD functionalized liposomes encapsulating urokinase for thrombolysis

Zhang, Nengpan (School of Nano Technology and Nano Bionics, University of Science and Technology of China, Hefei 230026, China ) ; Li, Chunlin (CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China ) ; Zhou, Dayong (Department of Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215002, China ) ; Ding, Chen (China Pharmaceutical University, Nanjing 211198, China ) ; Jin, Yaqing (CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China ) ; Tian, Qingmei (School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China ) ; Meng, Xiangzhou (School of Nano Technology and Nano Bionics, University of Science and Technology of China, Hefei 230026, China ) ; Pu, Kefeng (CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China ) ; Zhu, Yimin (CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Na ) ;
  • 초록  

    Abstract Thrombosis, a critical event in blood vessels, not only is associated with myocardial infarction and stroke, but also accounts for considerable morbidity and mortality. Thrombolytic drugs are usually applied to the treatment of acute myocardial infarction, acute cerebral infarction and pulmonary embolism. However, thrombolytic drugs show limited efficacy in clinical practice because of the short half-life in plasma and systemic side effects. In this study, the cyclic RGD (cRGD) functionalized liposomes were prepared to encapsulate urokinase, a cheap and widely used thrombolytic drug in clinic and better thrombolysis efficacy was achieved. The flow cytometry analysis showed that the cRGD liposomes could bind to the activated platelets while not to the resting platelets. In vitro release study revealed that the release percentage reached plateau in about 5 h with 60% urokinase being released from liposomes. Results from the in vitro thrombolysis experiments demonstrated a good thrombolysis potential of the cRGD urokinase liposomes. The in vivo thrombolysis study demonstrated that the cRGD liposomes could significantly reduce the dose of urokinase by 75% while achieving the equivalent thrombolysis effect as the free urokinase in mouse mesenteric thrombosis model. In conclusion, the cRGD liposomes encapsulating urokinase hold great promise in clinic for better thrombolytic efficacy. Statement of Significance In this paper, the cRGD liposomes were prepared to encapsulate urokinase for targeted thrombolysis therapy. The cRGD liposomes could specifically bind to the activated platelets and could stably and continuously release its loaded urokinase. The mouse mesenteric thrombosis model was established to evaluate the thrombolysis effect of the cRGD urokinase liposomes. The results demonstrated that the cRGD liposomes could improve the thrombolytic efficacy by almost 4-fold over free urokinase. In conclusion, the cRGD liposomes encapsulating urokinase had great potential for the clinical treatment of thrombosis. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    cRGD liposomes .   Urokinase .   Platelet targeting .   Thrombosis mouse model .   Thrombolysis.  

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