Delivering urokinase-type plasminogen activator using mulberry leaf exosomes enables thrombolysis and remodeling of venous microenvironments.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE
    • Publication Information:
      Publication: Amsterdam : Elsevier
      Original Publication: Guildford, Eng., IPC Science and Technology Press.
    • Subject Terms:
      Morus*/chemistry ; Plant Leaves*/chemistry ; Exosomes*/metabolism ; Urokinase-Type Plasminogen Activator*/metabolism; Animals ; Mice ; Humans ; Venous Thrombosis/drug therapy ; Venous Thrombosis/metabolism ; Drug Carriers/chemistry ; Thrombolytic Therapy/methods ; Reactive Oxygen Species/metabolism
    • Abstract:
      In the treatment of thrombosis, conventional nanocarriers inevitably have problems, such as adverse reactions and difficulties in synthesis. Inspired by the concept of 'medicine food homology,' we extracted and purified natural exosomes from mulberry leaves as carriers for the delivery of urokinase-type plasminogen activator (uPA) for targeted therapy. The obtained mulberry leaf exosomes (MLE) possessed a desirable hydrodynamic particle size (119.4 nm), a uniform size distribution (polydispersity index = 0.174), and a negative surface charge (-23.3 mv). Before loading with uPA, MLE were grafted with cyclic RGD (cRGD) to selectively bind activated platelets for thrombus targeting. The cytometry studies revealed that MLE@cRGD has a high thrombus targeting ability about 74.3 %. Animal tests demonstrated that the delivered uPA could dissolve clots almost completely in femoral vein thrombosis models. In addition, MLE could remodel venous microenvironments by effectively eliminating reactive oxygen species (ROS) and promoting the phenotypic transformation of macrophages from M1 to M2 for venous tissue repair.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Macrophage; Mulberry leaf exosomes; Reactive oxygen species; Thrombolysis; Urokinase-type plasminogen activator
    • Accession Number:
      EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
      0 (Drug Carriers)
      0 (Reactive Oxygen Species)
    • Publication Date:
      Date Created: 20241025 Date Completed: 20241203 Latest Revision: 20241203
    • Publication Date:
      20241204
    • Accession Number:
      10.1016/j.ijbiomac.2024.136866
    • Accession Number:
      39454913