BACKGROUND AND PURPOSE Emodin [1,3, has been reported to exhibit vascular anti-inflammatory properties. However, the corresponding mechanisms are not well understood. The present study was designed to explore the molecular target(s) of emodin in modifying lipopolysaccharide (LPS)-associated signal transduction pathways in endothelial cells. EXPERIMENTAL APPROACHCultured primary human umbilical vein endothelial cells (HUVECs; passages 3-5) were pre-incubated with emodin (1-50 mg·mL KEY RESULTSEmodin inhibited, concentration-dependently, the expression of LPS-induced pro-inflammatory cytokines (IL-1b, IL-6) and chemokines (IL-8, CCL2) and, in parallel, inhibited NF-kB activation and IkBa degradation in HUVECs. However, emodin did not inhibit the NF-kB activation and IkBa degradation induced by IL-1b. The cholesterol binding agent, MBCD, inhibited LPS-induced NF-kB activation in passaged HUVECs [which also lack the LPS receptor, membrane CD14 (mCD14)], showing that lipid rafts played a key role in LPS signalling in mCD14-negative HUVECs. Moreover, emodin disrupted the formation of lipid rafts in cell membranes by depleting cholesterol. CONCLUSIONS AND IMPLICATIONSLipid rafts were crucial in facilitating inflammatory responses of mCD14-negative HUVECs to LPS. Emodin disrupted lipid rafts through depleting cholesterol and, consequently, inhibited inflammatory responses in endothelial cells. AbbreviationsELISA, enzyme-linked immunosorbent assay; HUVECs, human umbilical vein endothelial cells; IkB, inhibitor of NF-kB;
The application of nanotechnology to biomedical research is expected to have a major impact leading to the development of new types of diagnostic and therapeutic tools. One focus in nanobiotechnology is to develop safe and efficient drug/gene delivery vehicles. Research into the rational delivery and targeting of pharmaceutical, therapeutic and diagnostic agents is at the forefront of projects in nanomedicine. Silica, as a major and natural component of sand and glass, is a versatile material due to the variety of available chemical and physical modifications that are available, and recently have been widely applied in nanobiotechnology as drug/gene carriers or fluorescent nano-probes. The goal of this brief review is to illustrate selected examples of various functionalized silica nanoparticles as drug/gene delivery systems that have been applied to the arenas of human disease therapy or detection (molecular and cellular imaging).
Aim: To determine the effects of ultrasound exposure in combination with a microbubble contrast agent (SonoVue) on the cellular uptake and delivery of drugs/genes into human umbilical vein endothelial cells (HUVECs) as well as their biological effects on migration. Methods: HUVECs in suspension were exposed to pulsed ultrasound with a 10% duty cycle in combination with various concentrations of a microbubble contrast agent (SonoVue) using a digital sonifier at a frequency of 20 kHz and an intensity of 3.77 W/cm 2 on the surface of a horn tip. Cell culture inserts were used to determine the cell migration ability. Results: Exposure to pulsed ultrasound resulted in enhanced green fluorescent protein (EGFP) gene transfection efficiencies ranging from 0.2% to 2%. The transfection efficiency of HUVECs was approximately 3-fold higher in the presence of SonoVue than in its absence at the effective exposure time of 6 s. For drug delivery to HUVECs using ultrasound, the delivery efficiencies of a lowmolecular-weight model drug (TO-PRO ® -1, M W 645.38) were significantly higher when compared to drug delivery without ultrasound, with a maximum efficiency of approximately 34%. However, the delivery efficiencies of a high-molecular-weight model drug (DextranRhodamine B, M W 70 000) were low, with a maximum delivery efficiency of nearly 0.5%, and gene transfection results were similarly poor. The migration ability of HUVECs exposed to ultrasound was also lower than that of the control (no exposure). Conclusion: The use of low-frequency and low-energy ultrasound in combination with microbubbles could be a potent physical method of increasing drug/gene delivery efficiency. This technique is a promising nonviral approach that can be used in cardiovascular disease therapy.
The use of nanotechnology in drug delivery is a rapidly expanding field. Biodegradable or nontoxic nanomaterials have the most promising application potentials in nanomedicine. Herein, we report a novel core-shell nanoparticle with double shell coatings (silica and poly(D,L-lactide-co-glycolide) (PLGA)) with the total shell thickness of (8.7 ± 1.3) nm. The outer shell of PLGA is biodegradable and used for controlled and sustained release, and the inner shell of silica is mesoporous for the preservation of the chemical radiation therapeutic of methyl viologen (MV), an oxidant that produces reactive oxygen species during cancer radiation therapy. The dissolution time course data and transmission electron microscopy images showed that the novel nanoparticles (Au@SiO 2 &PLGA) have been successfully prepared, and silica and PLGA coated well the gold (Au) template surfaces. Nanocapsules (MV@SiO 2 &PLGA) were obtained after the gold templates were dissolved using sodium cyanide. The sustained release property was characterized through detecting fluorescence quenching time course of fluorescent isothiocyanate after mixing with MV@SiO 2 &PLGA nanocapsules that encapsulate MV molecules. The sustained release of MV molecules could be extended to approximately four weeks. This novel delivery system has high potential in future application for the delivery of therapeutic drugs, particularly for the treatment of cancer by radiation therapy. nanoparticles, PLGA, silica, methyl viologen, drug delivery Citation:Yang H, Miyoshi H, Lou C C, et al. Preparation, characterization and release of methyl viologen from a novel nanoparticle delivery system with double shells of silica and PLGA.
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