**1. Introduction**

Reactive oxygen species (ROS) are the result of the normal cell metabolism of living organisms. However, when the production of ROS exceeds the scavenging capacity of living organisms, oxidative stress occurs [1]. Excessive reactive oxygen species (ROS) not only affect normal metabolism, but also is closely related to the occurrence and development of various diseases, including cardiovascular diseases [2], Alzheimer's disease [3], nonalcoholic fatty liver disease [4], and so on. As an essential micronutrient for human health, selenium (Se) plays a vital role in protecting against oxidative stress [5]. Nevertheless, the beneficial and harmful doses of Se is an extremely narrow margin, which limits its practical applications in food and medicine [6]. Therefore, it is necessary to take effective measures to solve this problem.

Nanotechnology, as a technology developed in recent years, has been widely used in the field of biology. Selenium nanoparticles (SeNPs) have been widely used as drug

**Citation:** Chen, J.; Chen, X.; Li, J.; Luo, B.; Fan, T.; Li, R.; Liu, X.; Song, B.; Jia, X.; Zhong, S. Preparation and Characterization of Nano-Selenium Decorated by Chondroitin Sulfate Derived from Shark Cartilage and Investigation on Its Antioxidant Activity. *Mar. Drugs* **2022**, *20*, 172. https://doi.org/10.3390/ md20030172

Academic Editors: Donatella Degl'Innocenti and Marzia Vasarri

Received: 3 February 2022 Accepted: 24 February 2022 Published: 26 February 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

carriers due to their advantages of small volume, large specific surface area, and unique physical and chemical properties. Previous studies have found that SeNPs can remove harmful peroxides from the body through glutathione peroxidase (GSH-PX) and protect the membrane structure of the body from damage [7]. Meanwhile, compared with organic and inorganic selenium compounds [8], SeNPs possesses higher bioactivity like antioxidant activity, better bioavailability and lower toxicity [9]. However, SeNPs are very unstable in the liquid phase and tend to aggregate and form gray or black selenium with a large particle size, thus losing the bioavailability and bioactivity of SeNPs [10]. Therefore, a suitable stabilizer is needed to improve its stability.

Natural bioactive polysaccharides have attracted more and more attention because they are rich in hydrophilic groups, such as hydroxyls, and are considered as ideal templates for SeNPs stabilization. A variety of polysaccharides have been reported to modify SeNPs and the modified SeNPs have been found to have strong antioxidant activity [6,11,12]. Chondroitin sulfate (CS), a natural anionic glycoaminoglycan, is extracted from various marine animal cartilages, such as shark, skate and so on [13,14]. Studies showed CS exhibited a variety of biological activities, such as antioxidant activity [15], anti-inflammatory activity [16] and anti-tumor activity [17]. Since it is rich in carboxyl and hydroxyl groups, it is often used to stabilize SeNPs. For example, Han et al. reported the preparation method of selenium–chondroitin sulfate (SeCS) using CS as a stabilizer to stable SeNPs, but the Se content in SeCS is only 10.1%, and the study on its stability has not been reported [18]. Since the Se content and stability of SeCS are related to its biological activity, it is necessary to further improve the Se content and investigate the stability of SeCS. Therefore, in this study, we screened the preparation conditions of SeCS, investigated its stability at a different pH and temperature, and evaluated its antioxidant activity using 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2- -azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) assays. This study provides a theoretical basis for the application of SeCS as a fresh antioxidant agent in food and medicine.
