Targeted nanoparticles triggered by plaque microenvironment for atherosclerosis treatment through cascade effects of reactive oxygen species scavenging and anti-inflammation.

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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:
      Reactive Oxygen Species*/metabolism ; Curcumin*/pharmacology ; Curcumin*/chemistry ; Atherosclerosis*/drug therapy ; Nanoparticles*/chemistry ; Anti-Inflammatory Agents*/pharmacology ; Anti-Inflammatory Agents*/chemistry ; Plaque, Atherosclerotic*/drug therapy; Animals ; Mice ; Humans ; Thioctic Acid/chemistry ; Thioctic Acid/pharmacology ; Heparin, Low-Molecular-Weight/pharmacology ; Heparin, Low-Molecular-Weight/chemistry ; Heparin, Low-Molecular-Weight/therapeutic use ; Mice, Inbred C57BL ; Inflammation/drug therapy ; Endothelial Cells/drug effects ; Endothelial Cells/metabolism ; Male ; P-Selectin/metabolism ; Drug Carriers/chemistry ; Antioxidants/pharmacology ; Antioxidants/chemistry
    • Abstract:
      Inflammatory factors and reactive oxygen species (ROS) are risk factors for atherosclerosis. Many existing therapies use ROS-sensitive delivery systems to alleviate atherosclerosis, which achieved certain efficacy, but cannot eliminate excessive ROS. Moreover, the potential biological safety concerns of carrier materials through chemical synthesis cannot be ignored. Herein, an amphiphilic low molecular weight heparin- lipoic acid conjugate (LMWH-LA) was used as a ROS-sensitive carrier material, which consisted of injectable drug molecules used clinically, avoiding unknown side effects. LMWH-LA and curcumin (Cur) self-assembled to form LLC nanoparticles (LLC NPs) with LMWH as shell and LA/Cur as core, in which LMWH could target P-selectin on plaque endothelial cells and competitively block the migration of monocytes to endothelial cells to inhibit the origin of ROS and inflammatory factors, and LA could be oxidized to trigger hydrophilic-hydrophobic transformation and accelerate the release of Cur. Cur released within plaques further exerted anti-inflammatory and antioxidant effects, thereby suppressing ROS and inflammatory factors. We used ultrasound imaging, pathology and serum analysis to evaluate the therapeutic effect of nanoparticles on atherosclerotic plaques in apoe -/- mice, and the results showed that LLC showed significant anti-atherosclerotic effects. Our finding provided a promising therapeutic nanomedicine for the treatment of atherosclerosis.
      (© 2024. The Author(s).)
    • References:
      Oxid Med Cell Longev. 2017;2017:8526438. (PMID: 29317985)
      J Control Release. 2023 Feb;354:294-304. (PMID: 36638843)
      Circ Res. 2015 May 22;116(11):1783-99. (PMID: 25999419)
      Nat Rev Immunol. 2013 Oct;13(10):709-21. (PMID: 23995626)
      Medicine (Baltimore). 2023 Jan 6;102(1):e32596. (PMID: 36607865)
      Angew Chem Int Ed Engl. 2023 Aug 14;62(33):e202304465. (PMID: 37338457)
      Bioact Mater. 2022 Apr 07;19:115-126. (PMID: 35475030)
      Clin Chim Acta. 2013 Sep 23;424:245-52. (PMID: 23782937)
      Colloids Surf B Biointerfaces. 2017 Sep 1;157:268-279. (PMID: 28601755)
      ACS Nano. 2018 Sep 25;12(9):8943-8960. (PMID: 30114351)
      Circulation. 2002 Sep 17;106(12):1453-9. (PMID: 12234947)
      Adv Sci (Weinh). 2019 Jun 21;6(17):1900101. (PMID: 31508270)
      Nat Rev Cardiol. 2022 Apr;19(4):228-249. (PMID: 34759324)
      Circulation. 2021 May 18;143(20):1946-1948. (PMID: 33999663)
      Biochim Biophys Acta. 2012 May;1822(5):631-8. (PMID: 22019723)
      Pharmaceutics. 2020 Nov 05;12(11):. (PMID: 33167402)
      Small. 2023 Dec;19(49):e2303459. (PMID: 37607320)
      ACS Nano. 2020 May 26;14(5):5862-5873. (PMID: 32379416)
      Circulation. 2001 Apr 10;103(14):1863-8. (PMID: 11294804)
      Arterioscler Thromb Vasc Biol. 2023 Feb;43(2):323-329. (PMID: 36453276)
      Food Chem Toxicol. 2018 Mar;113:49-65. (PMID: 29360556)
      Biomaterials. 2022 Sep;288:121705. (PMID: 36002347)
      Int Immunopharmacol. 2023 Jul;120:110338. (PMID: 37210916)
      Circulation. 2003 Feb 25;107(7):947-53. (PMID: 12600905)
      ACS Biomater Sci Eng. 2019 May 13;5(5):2258-2270. (PMID: 33405777)
      Free Radic Biol Med. 2011 Sep 1;51(5):978-92. (PMID: 21627987)
      Prog Lipid Res. 2003 Sep;42(5):405-22. (PMID: 12814643)
      Acta Pharm Sin B. 2020 Sep;10(9):1769-1783. (PMID: 33088695)
      Nat Commun. 2020 May 26;11(1):2622. (PMID: 32457361)
      Nutrition. 2021 Feb;82:111041. (PMID: 33199187)
      J Am Coll Cardiol. 2014 Jan 7-14;63(1):1-11. (PMID: 24140662)
    • Grant Information:
      2020-jdyxzdzk-03 Key Medical Specialty in Jiading District, Shanghai; U23A2096 and 52350710203 National Natural Science Foundation of China; 21490711500, 20DZ2254900, and 23WZ2503300 Science and Technology Commission of Shanghai Municipality; BP0719035 Shanghai Education Commission through the leading talent program, and the 111 Project; 21ZR1451400 Natural Science Foundation of Shanghai; 202240235 Shanghai Health and Family Planning Commission Fund; 2021-KY-10 Shanghai Jiading District Health and Family Planning Commission Fund
    • Contributed Indexing:
      Keywords: Atherosclerosis; Drug delivery; Lipoic acid; Low molecular weight heparin; Reactive oxygen species
    • Accession Number:
      0 (Reactive Oxygen Species)
      IT942ZTH98 (Curcumin)
      0 (Anti-Inflammatory Agents)
      73Y7P0K73Y (Thioctic Acid)
      0 (Heparin, Low-Molecular-Weight)
      0 (P-Selectin)
      0 (Drug Carriers)
      0 (Antioxidants)
    • Publication Date:
      Date Created: 20240726 Date Completed: 20240727 Latest Revision: 20240729
    • Publication Date:
      20240729
    • Accession Number:
      PMC11282716
    • Accession Number:
      10.1186/s12951-024-02652-9
    • Accession Number:
      39061065