Abstract
Backgroud. To evaluate improvement of arsenic trioxide-loaded PLGA nanoparticles (As2O3-PLGA-NPs) to Human Vascular Smooth Muscle Cells (HUVSMCs) in vitro. Methods. As2O3-PLGA-NPs were synthesized and characterized by transmission electron microscopy (TEM), scanning electron microscope (SEM), and energy dispersive spectrometry (EDS), and the cumulative release rates of As2O3-PLGA-NPs were measured in vitro; HUVSMCs were treated with As2O3-PLGA-NPs in vitro. MTT assay and flow cytometry assay (FCM) were performed to examine the inhibitory effect of As2O3-PLGA-NPs on HUVSMCs and compared with As2O3 solution at various concentrations. Optical microscope was used to observe the morphological change of HUVSMCs treated with As2O3-PLGA-NPs. The expression of Bcl-2, Bax, and MMP-9 in HUVSMCs was detected by RT-PCR and Western blot (WB). Results. EDS confirmed that prepared nanoparticles contained elements of arsenic. The surface coating of the eluting stent of As2O3-PLGA-NPs has the same characteristics with our self-prepared As2O3-PLGA-NPs, and it also has a drug sustained-release character. Compared with the control group, cell proliferation and migration cell were significantly suppressed with concentration-dependent ( P < 0.05 , respectively). Meanwhile, in concentration-dependent, As2O3-PLGA-NPs depressed mRNA and protein expression of Bcl-2 and MMP-9 and increased mRNA and protein expression of Bax. Conclusion. As2O3-PLGA-NPs had an inhibitory effect on HUVSMCs’ proliferation and migration, and it may work via regulating Bax, Bcl-2, and MMP-9 expression in vitro.
Highlights
Percutaneous coronary intervention (PCI) plays an important role in the treatment of coronary artery disease, there is still a risk of stent restenosis [1]
It was found in the experiment that both As2O3 and NP could inhibit the growth of Human Vascular Smooth Muscle Cells (HUVSMCs) and produce certain cytotoxicity and showed an obvious time and concentration-dependent relationship (P < 0:05)
MTT results showed that after 6 μM NP treatment for 3 days, it had an inhibitory effect on the proliferation of HUVSMCs, while its toxicity was the least
Summary
Percutaneous coronary intervention (PCI) plays an important role in the treatment of coronary artery disease, there is still a risk of stent restenosis [1]. Vascular smooth muscle cells (VSMCs) are a key part in intimal thickening of in-stent restenosis (ISR) [2, 3]. Arsenic compounds are natural substances that can effectively inhibit acute promyelocytic leukemia (APL) [4]. Related studies have shown that arsenic trioxide (As2O3) has a therapeutic effect on other types of malignant tumors [5,6,7]. As2O3 can effectively inhibit cell proliferation and has been widely used in clinical practice. The dosage forms of As2O3 were proposed [8, 9]
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