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

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • 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:
      Aortic Aneurysm, Abdominal*/drug therapy ; RNA, Small Interfering* ; Nanoparticles*/chemistry ; Mice, Inbred C57BL* ; Matrix Metalloproteinase 9*/metabolism; Animals ; Mice ; Male ; Polyphenols/chemistry ; Polyphenols/pharmacology ; Catechin/analogs & derivatives ; Catechin/chemistry ; Catechin/pharmacology ; Tea/chemistry ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 2/genetics ; Humans ; Macrophages/metabolism ; Macrophages/drug effects ; Gene Transfer Techniques ; Oxidative Stress/drug effects ; RAW 264.7 Cells ; Apoptosis/drug effects
    • 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).)
    • References:
      Eur Heart J. 2023 Aug 1;44(29):2682-2697. (PMID: 37387260)
      J Vasc Surg. 2018 Jan;67(1):2-77.e2. (PMID: 29268916)
      Eur Heart J. 2015 Nov 1;36(41):2779. (PMID: 26129948)
      J Am Coll Cardiol. 2018 Nov 27;72(21):2591-2605. (PMID: 30466517)
      Trends Cardiovasc Med. 2015 May;25(4):267-74. (PMID: 25435520)
      J Immunol. 2019 Feb 15;202(4):1176-1185. (PMID: 30642978)
      Arterioscler Thromb Vasc Biol. 2019 Aug;39(8):1652-1666. (PMID: 31294623)
      Interact Cardiovasc Thorac Surg. 2019 Mar 1;28(3):344-352. (PMID: 30169834)
      Biomedicines. 2022 Jan 02;10(1):. (PMID: 35052774)
      ACS Appl Mater Interfaces. 2022 Feb 2;14(4):5090-5100. (PMID: 35060376)
      Circ Res. 2019 Feb 15;124(4):607-618. (PMID: 30763207)
      Adv Sci (Weinh). 2023 Aug;10(24):e2302620. (PMID: 37349886)
      Br J Surg. 2019 Jul;106(8):1043-1054. (PMID: 31115915)
      Nat Rev Dis Primers. 2018 Oct 18;4(1):34. (PMID: 30337540)
      Acta Biomater. 2019 Sep 15;96:345-353. (PMID: 31306785)
      Arterioscler Thromb Vasc Biol. 2020 May;40(5):1352-1369. (PMID: 32212850)
      Circulation. 2020 Oct 6;142(14):1374-1388. (PMID: 33017217)
      Adv Mater. 2023 Jun;35(23):e2210691. (PMID: 36913720)
      Atherosclerosis. 2020 Mar;297:16-24. (PMID: 32059119)
      Ann Surg. 2023 Jun 1;277(6):912-919. (PMID: 36177847)
      Nat Rev Cardiol. 2017 Aug;14(8):457-471. (PMID: 28406184)
      Nat Rev Cardiol. 2019 Apr;16(4):225-242. (PMID: 30443031)
      Phytother Res. 2022 Feb;36(2):928-937. (PMID: 35132703)
      Eur J Radiol. 2024 Feb;171:111286. (PMID: 38215531)
      Atherosclerosis. 2013 Jan;226(1):29-39. (PMID: 23044097)
      Arterioscler Thromb Vasc Biol. 2019 Jan;39(1):e10-e25. (PMID: 30580562)
      Circ Res. 2015 Nov 6;117(11):e80-9. (PMID: 26443597)
      Eur J Vasc Endovasc Surg. 2024 Feb;67(2):192-331. (PMID: 38307694)
      Circulation. 2020 Aug 4;142(5):483-498. (PMID: 32354235)
      Eur J Vasc Endovasc Surg. 2016 Oct;52(4):487-499. (PMID: 27543385)
      Expert Rev Cardiovasc Ther. 2015;13(9):975-87. (PMID: 26308600)
      Arterioscler Thromb Vasc Biol. 2021 Apr;41(4):1534-1548. (PMID: 33535789)
      Folia Biol (Praha). 2017;63(5-6):209-216. (PMID: 29687775)
      Mol Ther. 2024 Feb 7;32(2):284-312. (PMID: 38204162)
      Circ Cardiovasc Imaging. 2023 Jan;16(1):e014615. (PMID: 36649454)
      Physiol Res. 2017 Dec 20;66(6):899-915. (PMID: 28937252)
      Arterioscler Thromb Vasc Biol. 2022 Oct;42(10):1244-1253. (PMID: 36073351)
      J Nanobiotechnology. 2022 Feb 19;20(1):88. (PMID: 35183183)
      J Vasc Surg. 2021 Jan;73(1):61-68. (PMID: 32330595)
      Circ Res. 2023 Feb 17;132(4):449-451. (PMID: 36795847)
      ACS Nano. 2022 Feb 22;16(2):2429-2441. (PMID: 35133795)
      Circulation. 2019 Mar 12;139(11):1381-1383. (PMID: 30855994)
      N Engl J Med. 2014 Nov 27;371(22):2101-8. (PMID: 25427112)
      ACS Nano. 2024 Feb 27;18(8):6650-6672. (PMID: 38369729)
      Eur Heart J. 2014 Nov 1;35(41):2873-926. (PMID: 25173340)
      Small. 2022 Jul;18(27):e2202604. (PMID: 35661593)
      Transl Res. 2023 Aug;258:72-85. (PMID: 36967061)
      Signal Transduct Target Ther. 2020 Jun 19;5(1):101. (PMID: 32561705)
      Eur J Vasc Endovasc Surg. 2024 Jul 23;:. (PMID: 39053643)
      J Vasc Surg. 2019 Mar;69(3):728-737. (PMID: 30301692)
      Cell Stem Cell. 2020 Apr 2;26(4):542-557.e11. (PMID: 32243809)
      Nat Commun. 2020 Nov 25;11(1):5994. (PMID: 33239616)
      Arterioscler Thromb Vasc Biol. 2019 Jun;39(6):1149-1159. (PMID: 30943775)
      J Am Coll Cardiol. 2020 Dec 22;76(25):2982-3021. (PMID: 33309175)
      JCI Insight. 2023 Sep 8;8(17):. (PMID: 37561588)
      Adv Mater. 2022 Nov;34(44):e2204455. (PMID: 36085560)
      J Vasc Surg. 2017 Jul;66(1):64-70. (PMID: 28216354)
    • 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