Inhibitory Effects of Docetaxel on Platelet-Derived Growth Factor (PDGF)-BB–Induced Proliferation of Vascular Smooth Muscle Cells Through Blocking PDGF-Receptor β Phosphorylation

Park, Eun Seok; Yoo, Jaeeun; Lim, Yong; Tudev, Munkhtsetseg; Yoo, Hwan‐Soo; Hong, Jin Tae; Yun, Young Won

doi:10.1254/jphs.10276fp

Cited by 24 publications

(27 citation statements)

References 52 publications

(41 reference statements)

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“…Despite these advancements, today's DES have not completely eradicated restenosis and still lead to a higher incidence of late stent thrombosis. Drug docetaxel (DTX) is a paclitaxel analogue with enhanced anti-proliferative ability and water solubility and has been shown to be a good candidate drug for the prevention of restenosis 9,10 . Thrombosis remains a concern after stent implantation, whether at the early or very late stage.…”

Section: Introductionmentioning

confidence: 99%

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

Wang

Huang

et al. 2018

NPG Asia Mater

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In this study, we designed a novel drug-eluting coating for vascular implants consisting of a core coating of the antiproliferative drug docetaxel (DTX) and a shell coating of the platelet glycoprotein IIb/IIIa receptor monoclonal antibody SZ-21. The core/shell structure was sprayed onto the surface of 316L stainless steel stents using a coaxial electrospray process with the aim of creating a coating that exhibited a differential release of the two drugs. The prepared stents displayed a uniform coating consisting of nano/micro particles. In vitro drug release experiments were performed, and we demonstrated that a biphasic mathematical model was capable of capturing the data, indicating that the release of the two drugs conformed to a diffusion-controlled release system. We demonstrated that our coating was capable of inhibiting the adhesion and activation of platelets, as well as the proliferation and migration of smooth muscle cells (SMCs), indicating its good biocompatibility and anti-proliferation qualities. In an in vivo porcine coronary artery model, the SZ-21/DTX drug-loaded hydrophobic core/hydrophilic shell particle coating stents were observed to promote re-endothelialization and inhibit neointimal hyperplasia. This core/shell particle-coated stent may serve as part of a new strategy for the differential release of different functional drugs to sequentially target thrombosis and in-stent restenosis during the vascular repair process and ensure rapid re-endothelialization in the field of cardiovascular disease.

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Section: Introductionmentioning

confidence: 99%

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

Wang

Huang

et al. 2018

NPG Asia Mater

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“…Consistent with the same concept, imatinib and carboplatin have enhanced efficiency in suppressing VEGF, PDGF and PDGF-Rα/ß expression in head and neck squamous cell carcinoma [90,91]. Docetaxel has been currently acclaimed as an inhibitor of PDGF; however, there are controversial findings, and future research is necessary to unveil opportunities and challenges in the standardization of therapy [92,93]. Bevacizumab has been used in combination with (PDGF aptamer, AX102) and displayed therapeutic efficacy [94].…”

Section: Pdgf As a Major Challenge In Translational Oncologymentioning

confidence: 88%

PDGF: the nuts and bolts of signalling toolbox

et al. 2011

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PDGF is a growth factor and is extensively involved in multi-dimensional cellular dynamics. It switches on a plethora of molecules other than its classical pathway. It is engaged in various transitions of development; however, if the unleashed potentials lead astray, it brings forth tumourigenesis. Conventionally, it has been assumed that the components of this signalling pathway show fidelity and act with a high degree of autonomy. However, as illustrated by the PDGF signal transduction, reinterpretation of recent data suggests that machinery is often shared between multiple pathways, and other components crosstalk to each other through multiple mechanisms. It is important to note that metastatic cascade is an intricate process that we have only begun to understand in recent years. Many of the early steps of this PDGF cascade are not readily targetable in the clinic. In this review, we will unravel the paradoxes with reference to mitrons and cellular plasticity and discuss how disruption of signalling cascade triggers cellular proliferation phase transition and metastasis. We will also focus on the therapeutic interventions to counteract resultant molecular disorders.

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“…In this study, stents with ADC may be an alternative solution for this problem. Anti-proliferative drugs DTX which can significantly inhibited the proliferation of VSMCs in a concentration-dependent manner 22 are only coated on the outer surface of stents to suppress neointima hyperplasia, while antithrombotics SZ-21which can bind platelet glycoprotein IIIa and inhibit platelet aggregation 23 coated on inner surface of stents may inhibit thrombus formation. Since endothelium could completely cover the inner surface of stent as early as possible, it will then decrease the possibility of ISR.…”

Section: Discussionmentioning

confidence: 99%

“…In the other aspect of anti-proliferation, DTX cumulative release has reached 18 mg/mL (approximately 20 μM) within 24 h and became the main release drug from 24 h to 7 d, which shows that ADC can significantly inhibit the proliferation of VSMCs. Because 10 μM docetaxel can significantly inhibit both the proliferation and the DNA synthesis of fetal bovine serum and plateletderived growth factor-BB-stimulated VSMCs in a concentration-dependent manner 22 . And in vitro cell proliferation assay, the PDC and ADC could significantly reduce VSMCs proliferation compared to the 316L SS stents after 3 d or 5 d co-culture, which indicated that DTX can potentially inhibit intimal hyperplasia and ISR caused by excessive VSMCs proliferation, migration to the intima and secretion of large amounts of extracellular matrix protein.…”

Section: Discussionmentioning

confidence: 99%

An asymmetrical dual coating on the stent prepared by ultrasonic atomization

et al. 2018

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This study aims to design an asymmetric dual coating (ADC) on the stent by ultrasonic atomization to solve the problem of delayed endothelialization and late or very late stent thrombosis which caused by drug eluting stent (DES) with symmetric coating. Chitosan loaded monoclonal platelet glycoprotein IIIa receptor antibody SZ-21 coating (CSC) was sprayed on inner surface of stents, and outer surface was sprayed CSC and poly(lactic-co-glycolic acid) (PLGA) loaded with docetaxel (DTX) coating (PDC). The coated surface was uniform without aggregation and no shedding phenomenon either before or after stent expanded. Fluorescence labeling has confirmed that the coating has an asymmetric structure. The cumulative release for SZ-21 and DTX was 40.11 % and 27.22 % within first 24 h, then DTX became the major released drug from 24 h to 7 d, after released for 28 d about 40% of the SZ-21 and 50% DTX still remained on the coated stent. It achieved that ADC can inhibit thrombosis at earlier period and inhibit vascular smooth muscle cells (VSMCs) proliferation at later period. And that ADC has good hemocompatibility and can significantly inhibit VSMCs proliferation. Finally, 4 and 12 weeks after the stent with ADC implanted into rabbit carotid arteries, it showed that the stent with ADC was safe and could effectively prevent thrombosis and in-stent restenosis.

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Inhibitory Effects of Docetaxel on Platelet-Derived Growth Factor (PDGF)-BB–Induced Proliferation of Vascular Smooth Muscle Cells Through Blocking PDGF-Receptor β Phosphorylation

Cited by 24 publications

References 52 publications

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

PDGF: the nuts and bolts of signalling toolbox

An asymmetrical dual coating on the stent prepared by ultrasonic atomization

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