**1. Introduction**

Bacterial infections are consistently ranked as one of the leading causes of human mortality, with infection rates, mortality rates, and hospitalization costs increasing annually [1–3]. The high prevalence of bacterial infections has led to the misuse of antibiotics, resulting in the emergence of superbugs as bacteria become resistant to treatment. Unfortunately, superbugs are arising at a rate much faster than that of new antibiotic discovery, thereby leading to a growing threat of untreatable bacterial infections [4–8]. Therefore, new treatments are urgently needed.

With the rapid development of technologies in the fields of modern nanotechnology and biomedicine, numerous antibacterial inorganic nanoparticles (NPs), such as silver, gold, copper nanoparticles, alumina, zinc oxide, magnesium oxide, silica titanium dioxide, and graphene oxide NPs, as well as their composites, have been used in antibacterial therapy [3,9–11]. For example, two-dimensional (2D) graphene-based nanocomposites and

**Citation:** Zhang, W.; Kuang, Z.; Song, P.; Li, W.; Gui, L.; Tang, C.; Tao, Y.; Ge, F.; Zhu, L. Synthesis of a Two-Dimensional Molybdenum Disulfide Nanosheet and Ultrasensitive Trapping of *Staphylococcus Aureus* for Enhanced Photothermal and Antibacterial Wound-Healing Therapy. *Nanomaterials* **2022**, *12*, 1865. https://doi.org/10.3390/ nano12111865

Academic Editor: Rosalia Bertorelli

Received: 22 April 2022 Accepted: 27 May 2022 Published: 30 May 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/).

analogues have been demonstrated to have wide application prospects because of their multi-functional antibacterial mechanisms, which include physical and chemical damage to bacterial cells [12,13]. Molybdenum disulfide (MoS2), a transition metal dichalcogenide, is similar to graphene. Currently, MoS2 has several potential applications in the field of biomedicine due to its unique electronic, optical, mechanical, and chemical properties, and MoS2 has been demonstrated to have unique optical properties in that it can convert itself into heat by absorbing light energy when irradiated with near-infrared (NIR) light. Through this property, MoS2 can kill bacteria [14–16].

Free MoS2 without irradiation does not have significant antibacterial effects. To improve the antibacterial ability of MoS2, we selected vancomycin (Van). Van is a peptide antibiotic that can kill bacteria, such as *Staphylococcus aureus* (*S. aureus*), residing on a wound's surface [17,18]. Van has an attractive property in that it can target bacteria through hydrogen bonding to the terminal D-Ala-D-Ala sequence of the cytosolic peptide unit of Gram-positive bacteria. In other words, Van recognizes the D-Ala-D-Ala sequence on the cell surface of bacteria, increasing the half-life and effective working radius of the nanoantibacterial composites and enhancing the antibacterial effect [19–22]. Together, MoS2 and Van can target Gram-positive bacteria, which can further enhance the thermal response of MoS2 and promote bacterial growth inhibition while applying antibiotic therapy. Van has a primary amine group that binds covalently to fluorescein 5(6)-isothiocyanate (FITC), and we selected FITC-labeled Van because it can maintain both the fluorescent properties of FITC and the ability of Van to bind to the bacterial cell wall, thereby facilitating subsequent experimental validation.

To promote wound healing, it is important not only to clean the wound of germs but also to maintain an environment that is suitable for healing. A moist and clean environment accelerates the migration of epidermal cells, which facilitates skin cell granulation and division [23–25]. Polymer hydrogels are one of the most practiced soft-wet materials used for biomedical applications [26]. They can provide this type of environment for wounds, and thermosensitive hydrogels are easy to prepare. Chitosan (CS) is a biocompatible and weakly immunogenic material that can be degraded by enzymes in vivo, and the degradation products, namely oligosaccharides, are non-toxic. In addition, CS can enhance drug penetration by affecting the tightness between epithelial cells, which makes CS a valuable entity in the biomedical field [27]. As such, we prepared a temperature-sensitive hydrogel excipient by wrapping our synthesized MoS2-Van-FITC nanomaterials, which possess photothermic and chemotherapeutic properties, in a hydrogel. By physically mixing CS with a sodium β-glycerophosphate (β-GP) solution, a sol-gel phase transition was achieved at temperatures higher than 37 ◦C due to the enhanced hydrogen bonding, electrostatic attraction, and hydrophobic interactions between CS and β-GP [28].

In this study (Figure 1), Van not only efficiently inhibited the growth of bacteria on the wound surface but also enhanced the antibacterial effect by targeting bacteria through hydrogen bonding with the terminal D-Ala-D-Ala sequence of the cytosolic peptide unit of Gram-positive bacteria, increasing the half-life of the composite and the effective working radius of the photothermal treatment. Therefore, when MoS2 is combined with Van, the effective working radius of MoS2 PTT can be further increased to better inhibit bacterial growth while applying anti-infective therapy. The covalent binding of primary amine groups using FITC with MoS2-Van confers the nanocomposite to maintain the fluorescent properties of FITC, which can be observed for real-time detection. Additionally, photothermal treatment combined with chemotherapy cleaned the wound surface of pathogenic bacteria, thereby accelerating wound healing.
