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

Abstract

Introduction 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.

Nanoparticles in the diagnosis and treatment of vascular aging and related diseases

“… 438 Numerous studies have shown that nanoparticles can be exploited to target and regulate vascular endothelial and VSMCs functions, including cell proliferation, migration, inflammation, senescence, and apoptosis. 36 , 339 , 439 – 441 There are particularly strong data indicating that proliferation and migration of endothelial dysfunction and VSMCs are vital to vascular aging-related diseases, such as atherosclerosis, hypertension, vascular stenosis and restenosis, and MI. 175 , 176 Therefore, nanoparticle-mediated anti-proliferation and anti-apoptotic therapies hold great promise in preventing vascular aging-related disorders.…”

“… 456 Wei et al packaged honokiol in MSNs and assembled them into honokiol-MSNs, and found that they effectively inhibited VSMCs proliferation and migration through alleviating Smad3 phosphorylation. 441 In another study, researchers employed layered double hydroxide (LDH) nanoparticles to deliver LMWH for the prevention of vascular restenosis, and found that LMWH-LDH nanoparticles were rapidly internalized by VSMCs and dramatically attenuated VSMCs proliferation and migration. 457 Notably, the application of 17β-estradiol (17-βE), ω-3-polyunsaturated fatty acids (PUFAs), and C6-ceramide (CER) in the treatment of vascular restenosis is limited by their extensive protein binding and lipophilicity.…”

Nanosystems in Cardiovascular Medicine: Advancements, Applications, and Future Perspectives

“…The honokiol-loaded MSNPs demonstrated inhibitory effects on the proliferation and migration of vascular smooth muscle cells (VSMCs) and effectively suppressed intimal thickening in a rat model of balloon injury. This nanosystem presents a promising strategy for preventing restenosis and enhancing the therapeutic potential of honokiol in the context of vascular interventions [ 39 ].…”

“…Additionally, drug-loaded nanoparticles show promise in the treatment of severe and life-threatening atherosclerotic lesions in coronary heart disease (CHD) [ 38 ]. Mesoporous silica nanoparticles (MSNPs) enhance the therapeutic effects of honokiol in inhibiting neointimal hyperplasia [ 39 ].…”

Molecular Action of Hydroxytyrosol in Attenuation of Intimal Hyperplasia: A Scoping Review

“…Alternatively, quercetin (Khandelwal et al, 2012) and salvianolic acid A (SAA) (Sun et al, 2012) were also found to inhibit proliferation of VSMCs too. Intriguingly, a green tea polyphenol, epigallocatechin-3-gallate (EGCg), suppressed neointimal hyperplasia (NIH) in rabbit model by inhibiting the proliferation of VSMCs via inactivation of MAPKs pathway In a recent study, Wei delivered mesoporous silica nanoparticles encapsulated honokiol (HNK), a small molecule polyphenol after balloon injury and HNK greatly suppressed intimal thickening by reducing phosphorylation of Smad3 (Wei et al, 2020).…”