Tea polyphenol nanoparticles enable targeted siRNA delivery and multi-bioactive therapy for abdominal aortic aneurysms.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, 2003-
    • Subject Terms:
    • Abstract:
      Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, while there is a lack of pharmaceutical interventions to halt AAA progression presently. To address the multifaceted pathology of AAA, this work develops a novel multifunctional gene delivery system to simultaneously deliver two siRNAs targeting MMP-2 and MMP-9. The system (TPNs-siRNA), formed through the oxidative polymerization and self-assembly of epigallocatechin gallate (EGCG), efficiently encapsulates siRNAs during self-assembly. TPNs-siRNA safeguards siRNAs from biological degradation, facilitates intracellular siRNA transfection, promotes lysosomal escape, and releases siRNAs to silence MMP-2 and MMP-9. Additionally, TPNs, serving as a multi-bioactive material, mitigates oxidative stress and inflammation, fosters M1-to-M2 repolarization of macrophages, and inhibits cell calcification and apoptosis. In experiments with AAA mice, TPNs-siRNA accumulated and persisted in aneurysmal tissue after intravenous delivery, demonstrating that TPNs-siRNA can be significantly distributed in macrophages and VSMCs relevant to AAA pathogenesis. Leveraging the carrier's intrinsic multi-bioactive properties, the targeted siRNA delivery by TPNs exhibits a synergistic effect for enhanced AAA therapy. Furthermore, TPNs-siRNA is gradually metabolized and excreted from the body, resulting in excellent biocompatibility. Consequently, TPNs emerges as a promising multi-bioactive nanotherapy and a targeted delivery nanocarrier for effective AAA therapy.
      (© 2024. The Author(s).)
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    • Contributed Indexing:
      Keywords: Gene delivery; Inflammatory vascular disease; Macrophage repolarization; Matrix metalloproteinases; Nanomedicine; ROS scavenging
    • Accession Number:
      0 (RNA, Small Interfering)
      EC 3.4.24.35 (Matrix Metalloproteinase 9)
      0 (Polyphenols)
      8R1V1STN48 (Catechin)
      BQM438CTEL (epigallocatechin gallate)
      0 (Tea)
      EC 3.4.24.24 (Matrix Metalloproteinase 2)
    • Publication Date:
      Date Created: 20240808 Date Completed: 20240809 Latest Revision: 20240811
    • Publication Date:
      20240812
    • Accession Number:
      PMC11308685
    • Accession Number:
      10.1186/s12951-024-02756-2
    • Accession Number:
      39118143