*Article* **Seed-Mediated Preparation of Ag@Au Nanoparticles for Highly Sensitive Surface-Enhanced Raman Detection of Fentanyl**

**Yazhou Qin \* , Binjie Wang, Yuanzhao Wu, Jiye Wang, Xingsen Zong and Weixuan Yao \***

Key Laboratory of Drug Prevention and Control Technology of Zhejiang Province, Zhejiang Police College, 555 Binwen Road, Hangzhou 310053, China; wangbinjie@zjjcxy.cn (B.W.); wuyuanzhao@zjjcxy.cn (Y.W.); wangjiye@zjjcxy.cn (J.W.); zongxingsen@zjjcxy.cn (X.Z.)

**\*** Correspondence: yazhouqin@zju.edu.cn (Y.Q.); yaoweixuan@zjjcxy.cn (W.Y.)

**Abstract:** Bimetallic nanoparticles have received extensive attention due to their unique physical and chemical properties, including enhanced optical properties, chemical stability, and better catalytic activity. In this article, we have successfully achieved the controllable preparation of Ag@Au nanoparticles via a seed-mediated growth method. By regulating the amount of seeds—silver nanospheres—we realized that Ag@Au nanoparticles gradually changed from spherical to a seaurchin-like structure. The structure and composition of the prepared nanoparticles were characterized via scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), and high-angle circular dark field scanning transmission electron microscopy (HAADF-STEM). In addition, we use the prepared Ag@Au nanoparticles as a substrate material for highly sensitive surface-enhanced Raman spectroscopy (SERS). Using 4-aminothiophenol (4-ATP) as the test molecule, we explored the SERS enhancement effects of Ag@Au nanoparticles with different structures. Furthermore, we used Ag@Au nanoparticles for SERS to detect the drug fentanyl, and realized the label-free detection of fentanyl, with the lowest detection concentration reaching 10−<sup>7</sup> M. This research not only provides a method for preparing bimetallic Ag@Au nanoparticles with different structures, but also provides a reference for the application of Ag@Au nanoparticles in the field of detection technology.

**Keywords:** Ag@Au nanoparticle; core–shell structure; sea-urchin-like structure; SERS; fentanyl
