International Journal of Nanomedicine (Jul 2020)

Honokiol-mesoporous Silica Nanoparticles Inhibit Vascular Restenosis via the Suppression of TGF-β Signaling Pathway

  • Wei X,
  • Fang Z,
  • Sheng J,
  • Wang Y,
  • Lu P

Journal volume & issue
Vol. Volume 15
pp. 5239 – 5252

Abstract

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Xiao Wei,1,* Zhiwei Fang,2,* Jing Sheng,1 Yu Wang,3 Ping Lu1 1Department of Geriatrics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, People’s Republic of China; 2Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China; 3Department of Cardiology, Shidong Hospital of Yangpu District, Shanghai 200438, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Wang; Ping Lu Email [email protected]; [email protected]: The main pathological mechanism of restenosis after percutaneous coronary intervention (PCI) is intimal hyperplasia, which is mainly caused by proliferation and migration of vascular smooth muscle cells (VSMCs). Our previous study found that honokiol (HNK), a small-molecule polyphenol, can inhibit neointimal hyperplasia after balloon injury, but its specific mechanism is still unclear. Moreover, poor water solubility as well as low bioavailability of honokiol has limited its practical use.Methods: We used mesoporous silica nanoparticles (MSNPs) as a standard substance to encapsulate HNK and then assemble into honokiol-mesoporous silica nanoparticles, and we investigated the effect of these nanoparticles on the process of restenosis after common carotid artery injury in rats.Results: We report a promising delivery system that loads HNK into MSNPs and finally assembles it into a nanocomposite particle. These HNK-MSNPs not merely inhibited proliferation and migration of VSMCs by reducing phosphorylation of Smad3, but also showed a higher suppression of intimal thickening than the free-honokiol-treated group in a rat model of balloon injury.Conclusion: To sum up, this drug delivery system supplies a potent nano-platform for improving the biological effects of HNK and provides a promising strategy for preventing vascular restenosis.Keywords: mesoporous silica nanoparticles, honokiol, vascular smooth muscle cells, TGF-β pathway, balloon injury, intimal thickening, restenosis

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