**1. Introduction**

Noble metal nanocrystals have received extensive attention due to their unique localized surface plasmon resonance characteristics. A large number of studies have reported the application of noble metal nanocrystals in the fields of sensing, catalysis, and detection [1–5]. The characteristics of metal nanomaterials depend largely on their size, structure, and composition. In the past few decades, much research has been devoted to the controllable preparation of noble metal nanocrystals with uniform morphology and size. Various preparation methods have been developed one after another, including the solvothermal method [6–8], electrochemical method [9,10], and photochemical method [11]. Many metal nanocrystals with various regular morphologies have also been prepared. For example, Mirkin et al. realized the transformation of silver nanocrystals from spherical to icosahedral [12]. Yan et al. successfully prepared branched gold nanocrystals with tunable local surface plasmon resonance (LSPR) characteristics, and used the prepared gold nanocrystals as a substrate to achieve quantitative detection of the heme concentration in the cytosol of human red blood cells [13]. By controlling the kinetics involved in the growth of preformed Rh cube seeds, Xia et al. achieved the synthesis of Rh nanocrystals, including cubes, cubic octahedrons, and octahedrons [14]. In addition to polyhedral nanocrystals with regular morphologies, researchers have found that nanomaterials with sharp protrusions and pores often exhibit specific properties. For example, core–satellite structures and sea-urchin-like

**Citation:** Qin, Y.; Wang, B.; Wu, Y.; Wang, J.; Zong, X.; Yao, W. Seed-Mediated Preparation of Ag@Au Nanoparticles for Highly Sensitive Surface-Enhanced Raman Detection of Fentanyl. *Crystals* **2021**, *11*, 769. https://doi.org/10.3390/ cryst11070769

Academic Editors: Raghvendra Singh Yadav, Anju and Kottakkaran Sooppy Nisar

Received: 8 June 2021 Accepted: 26 June 2021 Published: 1 July 2021

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**Copyright:** © 2021 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/).

structures with sharp protrusions promote electromagnetic field enhancement by generating multiple "hot spots". This phenomenon has also aroused the interest of a large number of researchers.

In addition, researchers have found that alloy nanomaterials with different elemental compositions have the advantages of various nanomaterials, and show better performance than single-element nanomaterials in various fields. The preparation and performance of bimetallic nanoparticles is now an exciting research area, because they provide a new way to change the properties of the particles by mixing two metals in one particle. Especially for two kinds of metal nanoparticles with different advantages, we can realize the combination of their advantages through the controllable preparation of bimetallic nanoparticles, and avoid their respective disadvantages. For example, for two metal nanomaterials—gold and silver—studies have shown that silver nanomaterials have a larger excitation window from blue to near-infrared—than gold nanoparticles (from red to near-infrared) [15]. In addition, it can be said that silver is a more effective optical material than gold. Due to its greater scattering contribution, which is related to the real part of its dielectric constant, the surface-enhanced Raman scattering (SERS) signal generated by silver is more than 100 times higher than that of similar gold nanostructures [16]. However, the size and shape of gold nanoparticles are easier to control, and have good chemical resistance—that is, higher biocompatibility [17]. Therefore, silver nanomaterials are used more in in vitro research, while gold nanoparticles are used more in in vivo research [18,19].

In order to make full use of the advantages of gold and silver nanoparticles, and avoid their disadvantages, we urgently need to develop an Ag@Au nanomaterial that can coat the surface of silver nanoparticles with a gold layer, or form an alloy of gold and silver on the surface of silver nanoparticles. In general, alloy nanoparticles are obtained via the simultaneous reduction of two metal precursors (Ag<sup>+</sup> and Au3+). Conversely, the controlled growth of the metal on the preformed colloidal surface produces good results if the inner metal (the metal forming the colloid) has a greater surface free energy than the metal on its surface. However, because the surface free energy of gold is greater than that of silver (1.128 and 0.923 Jm−<sup>2</sup> , respectively), it is easier to grow silver on the surface of gold nanoparticles. In fact, a number of studies have also reported that Au@Ag nanoparticles were obtained by growing silver layers on gold seeds [20,21]. For example, Xia et al. recently achieved regulation of the plasma performance of Au@Ag nanoparticles by adjusting the thickness of the silver layer grown on the surface of gold nanospheres and gold nanorods [22]. Cheng et al. adjusted the concentration of the surfactant cetyltrimethylammonium chloride (CTAC) to precisely control the position of the Ag coating on the convex gold nanoarrows. Three different nanostructures were obtained at low, medium, and high CTAC concentrations—namely, anisotropic coating, intermediate coating, and conformal coating, respectively [23]. Conversely, depositing gold onto silver nanoparticles by reducing gold precursors yields a solid solution of the two metals [24]. In general, the gold precursor will undergo a galvanic replacement reaction with the silver nanoparticles, so that the internal silver atoms are first replaced by silver ions, and then the silver ions are reduced to silver atoms by the reducing agent in the solution and deposited on the surface, so that the hollow structure is finally obtained [25–28]. As far as we know, only a few studies have reported the method of growing a gold layer on the surface of silver nanoparticles to prepare Ag@Au core–shell-structured nanoparticles. For example, Xia et al. successfully prepared Ag@Au nuclear sheath nanowires by depositing Au atoms on the surface of pre-synthesized Ag nanowires, which greatly improved their stability under different corrosive environmental conditions [29]. Kim et al. used sodium sulfite to selectively bind Au cations, and thereby reduce the reduction potential of Au (E ◦ = 0.111 V). The gold(I) sulfite complex is relatively benign to the Ag nanowire surface, so no oxidative etching will occur; on the contrary, the Au coating is promoted, and finally Ag@Au nanowires are formed [30]. Kim et al. achieved gold-spiked coating of silver particles through controlled Ostwald ripening of small gold nanoparticles on the surface of larger silver particles [31].

In this article, in order to fully combine the advantages of gold and silver nanoparticles and avoid their disadvantages, we have developed a method for preparing Ag@Au nanoparticles. Ag@Au nanoparticles have both the excellent surface plasmon resonance characteristics of silver nanoparticles and the stability of gold. First, Au3+ is combined with Br− in CTAB to form [AuBr4] <sup>−</sup>, and then the addition of ascorbic acid reduces Au3+ to Au<sup>+</sup> . Finally, an Au(I)–GSH complex is formed by combining Au<sup>+</sup> with glutathione modified on the surface of silver nanoparticles, and then Au<sup>+</sup> is reduced by glutathione in situ to grow gold on the surface of silver nanoparticles. By simply adjusting the amount of silver seeds added, we realized the transformation of the Ag@Au nanoparticle structure from spherical to a sea-urchin-like structure.
