Abstract
Oxidative stress can lead to permanent and irreversible damage to cellular components and even cause cancer and other diseases. Therefore, the development of antioxidative reagents is an important strategy to alleviate chronic diseases and maintain the redox balance in cells. Small-molecule bioactive compounds have exhibited huge therapeutic potential as antioxidants and anti-inflammatory agents. Myricetin (Myr), a well-known natural flavonoid, has drawn wide attention because of its high antioxidant, anti-inflammatory, antimicrobial, and anticancer efficacy. Especially regarding antioxidation, Myr is capable of not only chelating intracellular transition metal ions for removing reactive oxygen species, but also of activating antioxidant enzymes and related signal pathways and, thus, of sustainably scavenging radicals. However, Myr is poorly soluble in water, which limits its bioavailability for biomedical applications, and even its clinical therapeutic potential. The antioxidant peptide glutathione (GSH) plays a role as antioxidant in cells and possesses good hydrophilicity and biocompatibility. However, it is easily metabolized by enzymes. To take advantages of their antioxidation activity and to overcome the abovementioned limitations, GSH, Zn2+, and Myr were selected to co-assemble into Myr-Zn2+-GSH nanoparticles or nanoarchitectonics. This study offers a new design to harness stable, sustainable antioxidant nanoparticles with high loading capacity, high bioavailability, and good biocompatibility as antioxidants.
Highlights
Oxidative stress, caused by an imbalance between antioxidative and oxidative systems, leads to permanent and irreversible damage of cellular components, such as proteins, lipids, and nucleic acids [1]
2′7′-dichlorodihydrofluorescein diacetate (DCFH-DA) dye was used to incubate these cells for 5 min and the fluorescence intensity of the cells was recorded via confocal laser scanning microscopy
The co-assembly mechanism was further revealed through quantitative stoichiometry analysis
Summary
Oxidative stress, caused by an imbalance between antioxidative and oxidative systems, leads to permanent and irreversible damage of cellular components, such as proteins, lipids, and nucleic acids [1]. A plenty of disadvantages restrict biomedical applications, namely low biocompatibility of the metal-based nanomaterials, low bioavailability of hydrophobic small-molecule compounds, and easy degradation of antioxidant peptides by proteases. In spite of the tremendous potential, Myr possesses the same shortcomings as many hydrophobic small molecules, namely low bioavailability, poor water solubility and rapid degradation at pH > 6.8, which limits its clinical therapeutic potential [22]. The obtained MZG nanoparticles exhibit high loading capacity as well as good bioavailability and biocompatibility, leading to stable antioxidant effects. 10 mg·mL−1 of Myr was dispersed in 0.1 M NaOH, 10 mg·mL−1 of GSH was dispersed in deionized water, and a 100 mM solution of Zn2+ was prepared. MZG nanoparticles were produced by adding 100 μL of Myr into a mixed solution of 200 μL of GSH solution, 15.7 μL of Zn2+ solution and 684 μL of water. The concentration of Zn2+ was measured by inductively coupled plasma optical emission spectroscopy (ICP-OES)
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