MoS₂–Plasmonic Hybrid Platforms: Next-Generation Tools for Biological Applications

Abstract

The combination of molybdenum disulfide (MoS₂) with plasmonic nanomaterials has opened up new possibilities in biological applications by combining MoS₂’s biocompatibility and high surface area with the optical sensitivity of plasmonic metals. These MoS₂–plasmonic hybrid systems hold great promise in areas such as biosensing, bioimaging, and phototherapy, where their complementary properties facilitate improved detection, real-time visualization, and targeted therapeutic interventions. MoS₂’s adjustable optical features, combined with the plasmon resonance of noble metals such as gold and silver, enhance signal amplification, enabling detailed imaging and selective photothermal or photodynamic therapies while minimizing effects on healthy tissue. This review explores various synthesis strategies for MoS₂–plasmonic hybrids, including seed-mediated growth, in situ deposition, and heterojunction formation, which enable tailored configurations optimized for specific biological applications. The primary focus areas include highly sensitive biosensors for detecting cancer and infectious disease biomarkers, high-resolution imaging of cellular dynamics, and the development of phototherapy methods that allow for accurate tumor ablation through light-induced thermal and reactive oxygen species generation. Despite the promising advancements of MoS₂–plasmonic hybrids, translating these platforms into clinical practice requires overcoming considerable challenges, such as synthesis reproducibility, toxicity, stability in physiological conditions, targeted delivery, and scalable manufacturing. Addressing these challenges is essential for realizing their potential as next-generation tools in diagnostics and targeted therapies.

1. Introduction

The extensive use of nanoscale materials in biomedical science, biosensors, and biomolecular imaging for disease diagnosis, prevention, and treatment has attracted considerable interest from researchers [1,2,3,4,5,6,7]. The distinct properties of these materials—such as low toxicity, accurate targeting capabilities, and highly tunable features—make them well suited for various biomedical applications [8,9].

Nanomaterials can be categorized by dimensionality into zero-dimensional (0D), one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) structures [10]. Among these, 2D materials have attracted particular attention owing to their remarkable physicochemical properties and extensive potential applications. Their atomically thin layers provide thermal stability, mechanical strength, and flexibility [11,12,13], which are advantageous for biomedical and sensing applications.

Since the isolation of graphene in 2004 by Novoselov et al. [14], a diverse array of 2D nanomaterials, including black phosphorus, boron nanosheets, antimonene, and hexagonal boron nitride, has been investigated [15,16,17,18,19,20,21,22]. Transition metal dichalcogenides (TMDs), particularly molybdenum disulfide (MoS₂), have emerged as promising alternatives to graphene, presenting unique optical, electrical, and chemical properties that are advantageous for various biomedicine applications [23,24,25,26,27,28]. Nanostructured MoS₂-based biomaterial features a distinctive direct bandgap, strong near-infrared (NIR) absorbance, large surface area, and readily functionalizable sites, showing considerable potential in fields such as biosensing [29,30,31,32], bioimaging [33], phototherapy [34,35,36], drug delivery [37,38], and theranostics [39,40].

Moreover, the minimal cytotoxicity and excellent biocompatibility of MoS₂ provide additional advantages over graphene and other materials. Teo et al. conducted cell viability assessments on human lung carcinoma epithelial cells (A549) exposed to various concentrations of TMDs and graphene over 24 h [41]. The results showed that MoS₂ nanosheets maintained cell viability levels at least twice as high as those of graphene, even at concentrations 1.6 times greater than those of graphene. Notably, MoS₂ nanomaterials exhibited considerably fewer hazardous effects compared with graphene oxides and halogenated graphene, establishing MoS₂ as a more biocompatible option for potential biomedical applications.

While graphene’s zero-bandgap limits its suitability for electronic and optoelectronic applications, MoS₂ exhibits compelling properties, including a substantial direct bandgap of approximately 1.9 eV in its monolayer form. This bandgap is tunable and increases with decreasing number of layers, which is attributed to quantum confinement effects. Bulk MoS₂ has an indirect bandgap of approximately 1.2 eV, which transitions to a direct bandgap of approximately 1.9 eV when reduced to a monolayer. These unique characteristics make MoS₂ a highly attractive candidate, offering advantages over its counterparts for various biosensing applications. Similarly, black phosphorus-based photodetectors demonstrate exceptional photodetection capabilities owing to their suitable bandgap and high carrier mobility. However, their poor stability severely restricts their use in long-term photodetection applications [42].

Notably, the hybridization of MoS₂ with plasmonic materials (e.g., gold and silver nanoparticles) is a groundbreaking approach that merges the complementary properties of both components. MoS₂–plasmonic hybrids leverage the unique plasmonic features of metallic nanoparticles (NPs) to enhance electronic and optical signals, resulting in substantial improvements in sensitivity for biosensing and advanced imaging capabilities for super-resolution bioimaging. These hybrid platforms also facilitate localized surface plasmon resonance (LSPR)-based manipulation, creating new opportunities for real-time biological sensing and targeted therapeutics [43].

Regarding LSPR applications, a systematic study demonstrated that MoS₂ offers greater favorability than graphene [44]. MoS₂ exhibits robust light–matter interactions, which substantially enhance the sensitivity of biosensors when layered with gold nanoparticles (AuNPs). This configuration achieves sensitivity of up to 403 nm/RIU, highlighting MoS₂’s superior performance in molecular detection. Although graphene exhibits excellent electrical conductivity and absorption properties, its relatively low absorption per atomic layer (~2.3%) limits its effectiveness in enhancing sensitivity for LSPR applications. In contrast, MoS₂ exhibits stronger absorption, with an absorption per atomic layer of approximately 5%. Moreover, MoS₂’s compatibility in hybrid structures establishes it as a more effective choice for advancing LSPR technology, particularly for ultrasensitive biosensing applications.

This synergy between MoS₂ and plasmonic materials enhances their functional versatility, positioning them as ideal candidates for next-generation tools in biological applications, such as high-sensitivity biosensors, image-guided therapy, and diagnostic platforms. By combining MoS₂’s inherent biocompatibility with the signal-enhancing properties of plasmonic NPs, these hybrid materials offer promising solutions to complex biomedical challenges that require accurate detection and real-time imaging capabilities [45].

Previous studies have advanced our understanding of MoS₂ interactions with plasmonic nanostructures. While some reviews have focused on the synthesis and applications of noble metal nanostructure-decorated MoS₂ hybrids, this review aims to elucidate the mechanisms underlying the interactions between MoS₂ and plasmonic materials, highlighting their enhanced electronic, optical, and catalytic properties. In addition, this review addresses the challenges of harnessing the innovative potential of MoS₂–plasmonic hybrids as next-generation platforms for various biological applications.

2. MoS₂ Nanomaterials

2.1. MoS₂ Structure

Two-dimensional MoS₂ nanomaterials exist in different layer configurations and structural forms. A single-layer MoS₂ usually displays either an octahedral or a trigonal prismatic coordination phase, as shown in Figure 1 [46]. In multilayered MoS₂ nanostructures, each layer can independently assume either phase, resulting in a variety of polymorphic structures. The most prevalent polymorphs are trigonal (1T), hexagonal (2H), and rhombohedral (3R), with the numeral indicating the coordination number [46,47].

The 1T phase of MoS₂ displays metallic characteristics, while the 2H and 3R phases possess semiconducting properties, making them suitable for a range of electronic applications. Furthermore, both the 2H and 3R phases serve effectively as dry lubricants, and the nonlinear optical properties of the 3R phase enhance its applicability in nonlinear optical mass sensing, quantum measurements, and biomedicine [48]. Among the different stacking configurations, the 1H MoS₂ phase is the most stable, featuring a sandwich-like S–Mo–S structure, where each sulfur (S) layer is covalently bonded to a Mo layer, resulting in a thickness of approximately 0.65 nm [49]. The adjacent S–Mo–S layers are held together by weaker van der Waals forces [50]. The conductivity of MoS₂ is influenced by both temperature and thickness, generally increasing with temperature but decreasing as thickness increases, ultimately approaching the properties of bulk material [51].

MoS₂ exhibits remarkable versatility, appearing in two-dimensional structures (e.g., nanosheets, nanoribbons), one-dimensional configurations (e.g., nanowires, nanotubes), and zero-dimensional forms (e.g., quantum dots, nanoplatelets). For instance, 2D nanoribbons generally measure one to three layers in thickness, while one-dimensional nanowires (NWs) are approximately 14–30 nm in length and 0.6 nm in width [52]. Previously studied one-dimensional nanoplatelets range in size from 12 to 30 nm, with a width roughly equivalent to one unit cell, and demonstrate exceptional catalytic activity in hydrodesulfurization [53]. In contrast, quantum dots vary from 2 to 10 nm, possessing a larger bandgap than nanosheets and showcasing stronger Mo–Mo bonding compared to monolayers.

The transition of MoS₂ nanomaterials from two-dimensional to lower-dimensional structures results in changes to the bandgap, affecting both photoluminescence (PL) characteristics and optical properties. Monolayers and other low-dimensional forms of MoS₂ can seamlessly integrate into optical nanostructures, where light–matter interactions enhance PL intensity and emission rates [54,55,56]. These improvements underscore the potential of MoS₂ in advanced optical applications [33].

2.2. MoS₂ Properties

2.2.1. Electronic Properties

MoS₂ nanomaterials display unique electronic properties. In its bulk and multilayer forms, MoS₂ has an indirect bandgap, which increases as the number of layers decreases, ultimately reaching a direct bandgap of 1.8 eV in monolayer MoS₂ [57]. This inverse relationship between the bandgap and the number of MoS₂ layers is clearly shown in Figure 2 [58]. As shown in the first row of Figure 2, the bulk MoS₂ structure exhibits an indirect bandgap of approximately 1.2 eV, while the eight-layer configuration also maintains an indirect bandgap, following a similar energy trend. The six-layer MoS₂ structure still maintains an indirect bandgap. However, energy dispersion indicates modifications in electronic properties as the number of layers decreases. In the second row of Figure 2, the quadrilateral MoS₂ band structure transitions toward a direct bandgap with a clear separation between the valence and conduction bands. The MoS₂ bilayer further confirms this transition to a direct bandgap, with the gap increasing as the number of layers decreases. Finally, the MoS₂ monolayer reveals a direct bandgap of approximately 1.9 eV, highlighting the notable changes in electronic properties as the material transitions from bulk to monolayer. Comparatively, this direct bandgap remains higher than the 1.12 eV indirect bandgap of silicon [59], making MoS₂ a promising candidate for electronic applications.

2.2.2. Optical Properties

The optical properties of MoS₂, especially its absorption coefficient and refractive index (RI), are vital for optoelectronic applications. The absorption coefficient indicates the depth of light penetration before absorption and is high for MoS₂ in the 400–500 nm wavelength range, with a considerable decline occurring around 500 nm [60]. MoS₂’s adjustable bandgap, influenced by its size and structure, allows for tunable photoresponsivity, detectivity, and response time [61]. Both monolayer and multilayer MoS₂ structures demonstrate a high RI (>2), making them suitable for coatings.

Layer-dependent variations in the PL spectra of MoS₂ offer further insights into its optical characteristics. Due to its direct bandgap, MoS₂ efficiently absorbs photons with energies exceeding the bandgap. This results in a noticeable change in the PL spectra of ultrathin film MoS₂, particularly evident in monolayer MoS₂, as shown in Figure 3 [62,63,64,65]. This characteristic makes MoS₂ a promising candidate for optoelectronic applications [66].

Figure 3A–C provide detailed insights into the reflection and PL spectra of ultrathin MoS₂ and the layer-dependent effects on its PL efficiency. Notably, the ultrathin MoS₂ layer on a quartz substrate exhibited prominent peaks in both the reflection and PL spectra, corresponding to the MoS₂ absorption constant (Figure 3A). The absorption peaks at 1.85 eV (670 nm) and 1.98 eV (627 nm) are linked to the A₁ and B₁ direct excitonic transitions, resulting from the energy difference caused by spin–orbit coupling in the valence band. In the inset of Figure 3A, the band structure of bulk MoS₂, which omits the relatively weak effect of spin–orbit coupling, reveals an indirect bandgap around 1 eV and a distinct, higher-energy direct excitonic transition near the K point, indicated by an arrow. Figure 3B shows a pronounced PL response at the energies of direct excitonic transitions in monolayer MoS₂, which is lacking in the bulk MoS₂ sample because of its indirect bandgap. To further investigate the optical properties of MoS₂ nanomaterials, the layer-dependent PL efficiency of MoS₂ has been extensively studied, with spectra obtained for monolayer, bilayer, hexalayer, and bulk samples, as illustrated in Figure 3C,D [65]. Clear Raman peaks were detected for both MoS₂ and silicon vibrational modes. The Raman signal from thin-layer MoS₂, especially the monolayer, is relatively weak owing to the limited amount of excited material. However, despite this reduced material representation, monolayer MoS₂ demonstrates the highest PL intensity. An analysis of the PL spectra normalized by Raman intensity across different MoS₂ layer configurations reveals a substantial increase in luminescence efficiency in monolayer MoS₂.

2.2.3. Catalytic Properties

The catalytic behavior of MoS₂ is attributed to its layered structure, which offers accessible active sites such as edge sites, sulfur vacancies, and grain boundaries. Edge sites are particularly active for hydrogen evolution reaction (HER), providing favorable conditions for hydrogen adsorption and desorption [67]. Sulfur vacancies further enhance catalytic activity by increasing the number of adsorption sites, with optimal performance observed at a vacancy density of 7–10% [68,69]. The intrinsic turnover frequencies (TOFs) for different active sites show that edge sites are the most catalytically efficient, while sulfur vacancies offer moderate activity, and grain boundaries contribute minimally to HER activity, highlighting the critical role of edge sites in MoS₂’s catalytic performance.

Vijayan and Sandhyarani developed an innovative thermal processing method to synthesize a new heterostructure catalyst for HER based on MoS₂, specifically molybdenum disulfide–molybdenum trioxide–rhenium oxide (MoS₂–MoO₃–Re₂O₇) [70]. This composite is derived from bulk MoS₂, which is typically considered a weak catalyst for HER. However, the MoS₂–MoO₃–Re₂O₇ composite shows considerably enhanced catalytic performance compared to bulk MoS₂, as demonstrated by both electrochemical and photoelectrochemical studies. Mott–Schottky analysis indicates the formation of a p–n heterojunction, which improves interfacial contact and aids in the separation and movement of photogenerated charge carriers, thus increasing photoelectrocatalytic efficiency. The catalyst’s exceptional stability is further confirmed through extensive cycling tests.

Xu et al. performed a comprehensive analysis of MoS₂-based electrocatalysts for HER [71]. They found that the crystal structure, microstructure, surface, and interface of MoS₂ were critical factors in enhancing catalytic performance by modifying electrical conductivity, surface wettability, active site density, and changes in Gibbs free energy changes for hydrogen adsorption (ΔG_H). Additionally, surface and interface engineering—encompassing phase engineering, defect engineering, morphology design, and heterostructure development—are identified as advanced strategies for creating MoS₂-based catalysts that offer excellent efficacy at a low cost by optimizing surface-active sites, charge transfer, DGH, and surface hydrophilicity.

2.3. MoS₂ Functionalization for Biological Applications

To improve the properties of MoS₂ nanostructures for biological applications, various strategies for functionalization and surface modification have been developed. Commonly used approaches include both chemical and physical functionalization: chemical functionalization establishes new covalent bonds between the modifying agent and the substrate, while physical functionalization depends on interactions such as electrostatic attraction [72].

Following the synthesis of 2D MoS₂, thin sheets are functionalized to specifically target biological molecules, making them suitable for biosensor development. Surface functionalization leads to charge displacement and the formation of surface dipoles, which can considerably modify the electrical band structure of 2D MoS₂ [73]. Many studies have focused on functionalizing the basal plane of MoS₂; however, challenges arise owing to the absence of dangling bonds and the extensive van der Waals surface area, which favors physisorption over stronger covalent or ionic bonding [74]. This results in molecules lying flat on the MoS₂ surface, causing physisorption reactions that exhibit limited selectivity. However, by engineering the physisorbed layer, a selective surface for specific bioanalytes can be developed, thus enhancing the performance of biosensors.

Common approaches for modifying oxide and chalcogenide surfaces, such as silane and thiol-based techniques, are applicable to MoS₂ as well. These methods work by creating hydroxyl and thiol groups on molybdenum that is exposed owing to sulfur deficiencies on the basal plane [75]. The efficacy of these functionalization techniques depends on the presence of these sulfur deficits to reveal the molybdenum sites.

Additionally, the edges of 2D MoS₂ flakes, which can end with either metal or chalcogen atoms depending on the synthesis conditions, also present opportunities for functionalization [76]. Characteristics such as low-coordination step edges and kinks modify local surface effects and energies, which become more pronounced as the lateral dimensions decrease [77]. These features allow for the incorporation of functional groups, including hydroxyls and thiols, which can enhance bioactivity [78]. Moreover, disulfide bonds (R–S–S–C) can be used to attach organic molecules, such as proteins, while –SOH groups can promote interactions with proteins and carbohydrates.

Additional functionalization methods encompass in situ metal ion reduction, ring-opening polymerization, esterification, and free radical polymerization. According to Voiry et al., the covalent modification of metallic 1T MoS₂ with amide and methyl groups induces a phase transition from the metallic 1T phase to the semiconducting 2H phase [79].

Gómez-Muñoz et al. proposed an innovative method for covalently coating chemically exfoliated MoS₂ layers using functional polymer molecules [80]. This method uses a diazonium-anchored reaction, which facilitates the in situ radical polymerization of functional acrylate monomers, leading to the formation of a stable, homogeneous polymeric coating on the MoS₂ surface. The incorporation of fluorinated acrylate monomers during functionalization improves the hydrophobicity and stability of MoS₂, making it better suited for practical applications. This method not only simplifies the functionalization process but also ensures a high density of functional groups in the MoS₂ layers. The polymer-coated MoS₂ exhibited notable hydrophobic properties, with contact angles reaching 110° and 150° for different fluorinated acrylates. Additionally, polymer-coated MoS₂ exhibited enhanced resistance to oxidation compared with unmodified MoS₂. This functionalization approach not only enhances the material properties of MoS₂ but also expands its potential applications in fields like optoelectronics, sensing, and catalysis, highlighting the versatility of 2D materials through targeted surface modification. Despite its advantages, this covalent coating method has certain limitations. This method relies on specific chemical conditions and reagents, such as diazonium salts, which may not be universally available and require careful handling because of their reactive nature.

Gan et al. explored the modification of MoS₂ nanosheets with the organic molecule 6-(9H-carbazol-9-yl) hexane-1-thiol (CHT) to enhance their potential applications in nonlinear optics and optical limiting [81]. Although MoS₂ is a 2D material known for its unique properties, its low reactivity and poor solubility in organic solvents present considerable challenges for its practical applications. The synthesis process involved dispersing MoS₂ in N,N-dimethylformamide (and refluxing it with CHT, forming MoS₂–CHT nanosheets. The spectroscopic analysis confirmed successful covalent bonding between MoS₂ and CHT, which considerably improved MoS₂’s solution processability. The modified MoS₂–CHT materials exhibited enhanced nonlinear optical properties, particularly in the annealed MoS₂–CHT/poly(methyl methacrylate) film. This film exhibited the highest nonlinear absorption coefficient and imaginary third-order susceptibilities at specific wavelengths. Structural changes during annealing, including a phase transition from the metallic 1T to the semiconducting 2H phase, contributed to these improvements. This study demonstrates that covalent functionalization effectively addresses MoS₂’s solubility challenges, paving the way for the development of efficient optical limiters and other advanced photonic devices.

Functionality is also crucial for the stabilization of 2D MoS₂ in ionic solutions, such as phosphate-buffered saline (PBS), which is commonly used in biosensor applications. Stable suspensions of MoS₂ are critical for operation in these conditions [82]. Additionally, 2D MoS₂ remains stable during photocatalytic reactions, allowing the use of optical methods for surface functionalization without compromising its properties.

The medical and sensor applications of metal and metal oxide NPs [83,84,85,86] have led to the development of synthetic methods for creating MoS₂-based hybrids. The nanostructures of metals and metal oxides, known for their catalytic and electrical properties, are effectively embedded in MoS₂ nanofilms. The supporting matrix of MoS₂ provides uniform distribution and enhanced functionality of these nanostructures, resulting in improved conductivity and catalytic efficiency compared to unmodified MoS₂ [87].

3. Plasmonic Nanomaterials

Plasmonic phenomena arise when light of an appropriate wavelength interacts with the surface of noble metals at a dielectric interface, thereby exciting conduction electrons and inducing their oscillation. This synchronized oscillation of electrons, known as plasmon resonance, generally occurs in particles approximately 300 nm in size or smaller [88,89]. Plasmonic nanomaterials, primarily made up of noble metals such as Au, Ag, and Cu, are highly valued for their unique optical characteristics, particularly in biological and medical fields [90,91,92,93]. These materials exhibit LSPR and surface-enhanced Raman scattering (SERS), which facilitate strong interactions with light at select wavelengths, resulting in enhanced electromagnetic fields in their vicinity. Such attributes pave the way for applications in imaging, sensing, and therapeutic delivery [94]. Au, Ag, and Cu are well suited for plasmonic applications because of their high charge–carrier concentrations and strong light absorption capabilities in the visible and NIR ranges. In contrast, 2D nanomaterials, owing to their atomic thinness and lower carrier concentrations, typically display low absorption in these wavelengths. For example, single-layer graphene absorbs only approximately 2.3% of incident light across the visible to mid-infrared (MIR) spectrum [95,96]. However, moderately doped graphene can absorb as much as 40% of incident light in the terahertz (THz) frequency range, facilitating efficient light–matter interactions and allowing for a tunable plasmonic response in this region [97].

In plasmonic sensors, Au, Ag, and Cu are frequently used owing to their strong effects in the visible and NIR regions. In LSPR-based sensors, variations in the local RI resulting from analyte binding led to a shift in the absorption peak, allowing for highly sensitive detection. Meanwhile, in SERS-based sensors, molecules adsorbed on the metal surface interact with the amplified electromagnetic field, resulting in enhanced molecular sensitivity.

While the plasmonic effects of 2D nanomaterials have been studied for LSPR sensor applications, their limited absorption in the visible and NIR regions restricts their direct use in plasmonic sensors. Therefore, 2D nanomaterials are often paired with metal nanostructures to enhance sensor performance. This enhancement is achieved through various mechanisms. (1) The high surface area and numerous functional groups in 2D nanomaterials provide many active sites for molecular binding, strengthening sensor interactions. (2) π–π stacking with biomolecules: 2D nanomaterials can interact with the aromatic rings of biomolecules such as proteins and nucleic acids, enhancing analyte immobilization. (3) Protection against oxidation: 2D materials such as graphene, hexagonal boron nitride, and TMDs can protect plasmonic metals from oxidation, increasing stability and sensor longevity. (4) Enhanced electric field and charge transfer: A 2D nanomaterial layer amplifies the electric field at the metal interface and facilitates charge transfer between the plasmonic metal and probe molecules owing to its high carrier mobility, further enhancing sensor sensitivity. These enhancement mechanisms establish plasmonic nanomaterials, particularly in combination with 2D materials, as effective tools for biological and medical sensing applications.

3.1. Localized Surface Plasmon Resonance

LSPR is a foundational phenomenon driving many of the functions of plasmonic nanomaterials [98,99]. This unique optical response can be accurately controlled by manipulating the dimensions, morphology, and composition of NPs, thereby dramatically enhancing sensitivity in sensing and imaging applications. In biological settings, LSPR is extensively used in biosensing to detect biomolecular interactions at extremely low concentrations [100,101]. Additionally, LSPR enhances contrast and resolution in imaging, facilitating the detailed observation of cellular processes [102,103]. Moreover, LSPR plays a crucial role in photothermal therapy (PTT), where NPs convert light into heat to selectively target and eliminate cancer cells while minimizing damage to adjacent healthy tissue [104].

The LSPR phenomenon originates from the collective oscillation of conduction band electrons in noble metal NPs, leading to enhanced optical absorption [105,106]. The plasmonic characteristics of NPs are highly influenced by factors such as shape, size, anisotropy, RI, and the interaction between metallic and dielectric components [107,108]. By fine-tuning these parameters, the LSPR absorption peak of NPs can be accurately controlled, rendering them suitable for various plasmonic applications. Various geometries, such as core@shell (CS), core/shell@shell (CSS), and decorated nanosheets, can be engineered to optimize optical properties. The properties of NPs are elucidated using a range of analytical approaches [109], including the finite element method [110], finite-difference time-domain theory [111,112], Mie theory [113,114], discrete dipole approximation [115], and effective medium theories [116,117].

3.2. Surface-Enhanced Raman Scattering

SERS is a key application of plasmonic nanomaterials, providing a powerful method for molecular detection and analysis [118,119]. This technique leverages the intensified electromagnetic fields generated by LSPR to dramatically amplify the Raman signals of molecules adsorbed onto NP surfaces [120,121]. Unlike conventional techniques that depend on fluorescent labeling, SERS enables the elucidation of molecular composition and structure without the need for tags [122]. This label-free approach minimizes interference and enhances analytical accuracy. Furthermore, SERS facilitates real-time monitoring of dynamic biological processes, providing valuable insights into molecular interactions and cellular activities [123].

4. MoS₂–Plasmonic Hybrid Platforms

The integration of MoS₂ with plasmonic materials in hybrid platforms has attracted considerable research attention [42,124]. Recent breakthroughs in the synthesis of these hybrid nanostructures have highlighted their synergistic properties and diverse applications [125,126]. Notably, it has been demonstrated that manipulating the number of MoS₂ layers and the aggregate size of plasmonic NPs provides an effective strategy for tailoring the performance of TMD-based devices.

For instance, under both nonresonant and resonant excitation conditions, Nam et al. used PL spectroscopy, a widely used technique for evaluating device performance, to investigate the variations in electronic and optical properties based on the number of MoS₂ layers and the dimensions of the gold nanoparticle (AuNP) aggregate [127]. They observed that the PL intensity in monolayer MoS₂/AuNPs increased with larger aggregate sizes, irrespective of the excitation conditions. The strain induced by AuNPs leads to a red shift; however, as the aggregates increase in size, the influence of p-doping becomes more pronounced, resulting in a noticeable blue shift. In multilayer MoS₂/AuNPs, a decrease in PL intensity is observed under nonresonant excitation, while an increase is observed with resonant excitation, primarily attributed to p-doping and LSPR, respectively. Notably, the change in spectral shape resulting from resonant excitation is only clearly discernible in small aggregates of AuNPs in all layers.

4.1. Synthesis of MoS₂–Plasmonic Hybrid Platforms

A variety of methodologies are currently used to synthesize MoS₂–plasmonic hybrid platforms (Table 1), primarily relying on seed-mediated growth techniques and controlled combination strategies of plasmonic materials with MoS₂ nanostructures [128].

The majority of synthesis methods use MoS₂ seeds, adopting bottom-up approaches. A promising strategy for high-yield synthesis is the nanosheet-templated epitaxial growth of nanostructures. Huang et al. developed a solution-based method that uses 2D MoS₂ nanosheets to facilitate the epitaxial growth of Pd, Pt, and Ag nanostructures [129]. Their findings revealed that metal nanostructures on the MoS₂ (001) surface predominantly exhibited (111) and (101) orientations.

Shi et al. proposed a controlled wet chemical approach to grow AuNPs on chemical vapor deposition (CVD)-grown MoS₂ layers, demonstrating that the Au–MoS₂ hybrids are primarily formed through non-covalent bonding [130]. The morphology, density, and size distribution of the metal NPs could be accurately controlled by manipulating defect densities in the MoS₂ layers. Seed-mediated growth methods using MoS₂ seeds considerably enhance the efficiency of plasmonic nanostructures, with MoS₂ serving as a substrate for atomically distributed metal catalysts (ADMCs). In a systematic study, Shi et al. synthesized ADMCs by depositing non-noble single-atom metals onto chalcogen sites in MoS₂ layers, resulting in a diverse range of stable ADMCs, including Pt, Pd, Rh, Cu, Pb, Bi, and Sn. This method underscores the broad applicability of ADMCs in heterogeneous catalytic systems [131].

Table 1. Advantages and limitations of synthesis methods for MoS₂–plasmonic hybrid platforms.

Methods	Advantages	Limitations
CVD [128,130,132]	- High quality - Suitable for large-scale applications	- High equipment costs - Time-consuming
Hydrothermal synthesis [130]	- Eco-friendly - Cost-effective	- Requires precise temperature and pressure control - Time-consuming
Solution-based methods [130]	- Selective decoration of metal NPs - Allows processing at low temperatures	- Risk of nonuniform NP deposition - Limited scalability
Solution-phase epitaxial Growth [129]	- Controlled growth of noble metal structures - Well-defined interfaces	- Requires precise control of growth conditions - Potential for nonuniform growth
Site-specific electrodeposition [131]	- Precise control over catalyst placement	- Requires careful parameter optimization - Scalability challenges
In situ synthesis [133]	- Direct growth on MoS2 enhances interaction with substrates - Defects act as nucleation sites for improved dispersion	- Requires careful control over synthesis conditions - Potential variability in particle size and morphology
Mechanical exfoliation [129,130,131]	- Simple and reliable method for producing high-quality MoS2 - Effective for single-layer or few-layer materials	- Limited scalability for large-area applications - Labor-intensive with low yield
Liquid exfoliation [129,130,133]	- Scalable for large quantities - Can enhance material properties	- Results in mixtures of different sizes and thicknesses - Lower quality compared to CVD
Chemical etching [131,133]	- Facilitates selective material removal - Creates well-defined structures	- Involves hazardous chemicals - Difficult to control the etching process

Abbreviations: CVD, chemical vapor deposition; NP, nanoparticle.

Table 1. Advantages and limitations of synthesis methods for MoS₂–plasmonic hybrid platforms.

Methods	Advantages	Limitations
CVD [128,130,132]	- High quality - Suitable for large-scale applications	- High equipment costs - Time-consuming
Hydrothermal synthesis [130]	- Eco-friendly - Cost-effective	- Requires precise temperature and pressure control - Time-consuming
Solution-based methods [130]	- Selective decoration of metal NPs - Allows processing at low temperatures	- Risk of nonuniform NP deposition - Limited scalability
Solution-phase epitaxial Growth [129]	- Controlled growth of noble metal structures - Well-defined interfaces	- Requires precise control of growth conditions - Potential for nonuniform growth
Site-specific electrodeposition [131]	- Precise control over catalyst placement	- Requires careful parameter optimization - Scalability challenges
In situ synthesis [133]	- Direct growth on MoS2 enhances interaction with substrates - Defects act as nucleation sites for improved dispersion	- Requires careful control over synthesis conditions - Potential variability in particle size and morphology
Mechanical exfoliation [129,130,131]	- Simple and reliable method for producing high-quality MoS2 - Effective for single-layer or few-layer materials	- Limited scalability for large-area applications - Labor-intensive with low yield
Liquid exfoliation [129,130,133]	- Scalable for large quantities - Can enhance material properties	- Results in mixtures of different sizes and thicknesses - Lower quality compared to CVD
Chemical etching [131,133]	- Facilitates selective material removal - Creates well-defined structures	- Involves hazardous chemicals - Difficult to control the etching process

Abbreviations: CVD, chemical vapor deposition; NP, nanoparticle.

In redox reactions, AuNPs can be synthesized using exfoliated MoS₂ seeds as substrates for Au atom deposition [128,134]. MoS₂ nanosheets exhibit remarkable reduction capabilities in HAuCl₄ solutions, facilitating Au ion reduction and subsequent synthesis of Au/MoS₂ nanostructures by controlling reactant ratios of Au ions and MoS₂ seeds. Studies have demonstrated that defects in MoS₂ promote the in situ synthesis of plasmonic Au nanocrystals, where MoS₂ edges guide the epitaxial growth of these nanocrystals. The LaMer growth process and planar aggregation of Au/MoS₂ nanoseeds enable the formation of Au atomic layers on heterostructures [133].

Defective sites on MoS₂ also enhance the reduction of Au(III). Initial interactions between AuCl₄⁻ and the MoS₂ surface form a MoS₂/AuCl₄ redox pair, where Au(III) is reduced to AuNPs directly on MoS₂ nanosheets [135]. Thus, MoS₂ can serve as an electron donor in spontaneous redox reactions. Yuan et al. used atomic force microscopy to investigate Au(III) deposition on MoS₂, revealing that photogenerated electrons from MoS₂ under light irradiation considerably contributed to Au(III) reduction [136].

An alternative bottom-up strategy entails preparing metal NPs in advance and using them as templates for hybrid fabrication. Among these methods, CVD is commonly used for the epitaxial growth of MoS₂ layers [137]. CVD provides control over the thickness and morphology of MoS₂ nanostructures, as exemplified by Yang et al., who synthesized monolayer MoS₂ ribbons on high-Miller-index Au facet templates [132].

In another study, prepatterned Au seeds served as nucleation sites for MoS₂ monolayers, enabling geometric control via CVD. The seeding effect, resulting from the favorable formation energy of MoS₂ on Au surfaces, directed the growth of MoS₂ monolayers at these specific locations [138,139].

Shi et al. devised a novel technique to selectively grow AgNPs on atomically layered MoS₂ under continuous 808 nm laser irradiation. This laser-induced growth is driven by photothermal conversion rather than direct laser energy, with AgNPs enhancing MoS₂’s thermal storage and stability owing to the surface plasmon resonance properties of silver [140].

Garoli et al. proposed a reliable approach for fabricating hybrid plasmonic nanopores through the controlled deposition of MoS₂ flakes onto metallic apertures. This configuration offers localized plasmonic enhancement in the 2D nanopore, rendering it suitable for single-molecule sensing and sequencing in flow-through systems. Metallic NPs can further intensify electromagnetic field confinement by synchronizing their resonance with that of the nanopore, paving the way for solid-state nanopores with integrated plasmonic capabilities [141].

Zuo et al. introduced a groundbreaking technique for the non-thermal induction of photogenerated electrons in MoS₂, facilitating interactions with Ag and Pt metal cations [142]. These interactions lead to the reduction and subsequent in situ deposition of metal NPs onto MoS₂ nanosheets, forming metal–MoS₂ nanohybrids. Notably, this method requires only metal salts to provide the required cations, eliminating the need for additional chemical reagents and reducing the risk of introducing toxic byproducts or environmental contaminants. The characterization techniques used confirmed the formation of highly crystalline metal NPs on the MoS₂ nanosheets, demonstrating the doping effects of the metal NPs and the modifications made to the MoS₂ structure. Moreover, the Ag–MoS₂ hybrids exhibited exceptional SERS activity, with an enhancement factor of 1.32 × 10⁷ and a detection limit as low as 10⁻¹¹ M, indicating considerable potential for sensing chemical and biological molecules. Additionally, the Pt–MoS₂ hybrids exhibited excellent HER performance, characterized by a low Tafel slope of 25 mV/decade and a TOF of 11.15 H₂ s⁻¹ at 220 mV, highlighting their promising applications in future hydrogen production.

4.2. Biological Applications of MoS₂–Plasmonic Hybrid Platforms

4.2.1. MoS₂–Plasmonic Hybrid Platforms for Biosensing

The integration of 2D materials with plasmonic structures has opened promising avenues for various cutting-edge biomedical applications (

Table 2. Biological applications of MoS₂–plasmonic hybrid platforms.

Hybrid Platform	Application	Target
AuNPs on 2D MoS2 modified on the working carbon electrode of an SPE [143]	Detection of PSA, a biomarker associated with prostate cancer	PSA
Nonmetallic plasmonic MoS2 nanosheets [144]	DNA sensor for detecting the hepatitis C virus gene	Hepatitis C virus gene
Carboxyl-functionalized MoS2 (MoS2–COOH) in an SPR detection platform [145]	Detection of the SARS-CoV-2 spike protein (S protein)	SARS-CoV-2 spike protein
AuNBPs combined with a MoS2 semiconductor layer (AuNBPs@MoS2) [146]	Anticancer therapy	HeLa cancer cells
Composite nanoprobe (Ag@MoS2) comprising DNA–Ag nanoclusters adsorbed onto MoS2 nanosheets [147]	In situ fluorescence imaging and quantitative analysis of intracellular ATP levels	Intracellular ATP in HeLa cells
Bi/MoS2 heterojunction complex in a fibrin gel [148]	Antibacterial treatment for diabetic wounds	S. aureus and E. coli bacteria
MA with HAP and PDA [149]	Controlled drug release	Anticancer drug DOX and MCF-7 cancer cells
MoS2–AuNRs–aptamer NPs [150]	Selective photothermal therapy for antimicrobial action	MRPA
MoS2 and AuNRs dual PPTT nanoagent [45]	Synergistic cancer phototherapy	ICG for cancer treatment
MoS2@AuNRs (1T-MoS2 nanosheets with AuNRs) [151]	Synergistic photothermal and photodynamic antibacterial therapy	E. coli bacteria
PEG–MoS2–AuNP hybrids loaded with Ce6 [152]	Stepwise photothermal and photodynamic therapy for cancer treatment	Tumor cells
Fe3O4@MoS2–Ag nanozyme [153]	Enhanced antibacterial therapy	E. coli bacteria
NFs with AuAg alloyed NPs [154]	Photothermal-assisted catalytic reaction	Reduction of 4-NiP to 4-AP

Abbreviations: ATP, adenosine triphosphate; PSA, prostate-specific antigen; SPE, screen-printed electrode; AuNBPs, gold nanobipyramids; AuNRs, gold nanorods; DOX, doxorubicin hydrochloride; MA, MoS₂@AuNRs nanoparticles; HAP, hydroxyapatite; PDA, polydopamine; MRPA, multidrug-resistant pseudomonas aeruginosa; ICG, indocyanine green; PPTT, plasmonic photothermal therapy; Ce6, chlorin e6; NFs, MoS₂ nanoflowers; NiP, nitrophenol; AP, aminophenol; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; HeLa, Henrietta Lacks; MCF-7, Michigan Cancer Foundation-7; NP, nanoparticle.

). MoS₂, known for its exceptional electronic properties, extensive surface area, and biocompatibility, is ideally suited for biosensing applications. By combining MoS₂ with plasmonic materials that exhibit LSPR, these hybrid platforms can dramatically enhance signal detection and sensitivity.

Yaiwong et al. devised a dual-mode immunosensor that combines SERS with electrochemical (EC) techniques to detect prostate-specific antigen (PSA), a biomarker associated with prostate cancer [143] (Figure 4). This sensor uses a hybrid of AuNPs on 2D MoS₂, modified on the working carbon electrode of an SPE. A primary antibody (Ab1) is immobilized on the modified electrode, forming an Ab1/Au@MoS₂/SPE structure for specific PSA recognition. Simultaneously, AuNPs are conjugated with a secondary antibody (Ab2) and the probe molecule 3,3′,5,5′-tetramethylbenzidine (TMB), creating nanotags (TMB/Ab2/AuNPs) that exhibit strong SERS and EC responses. When PSA is present, sandwich immunocomplexes form through antigen–antibody interactions (Ab1–PSA–Ab2). Differential pulse voltammetry is used for EC detection, while SERS data are acquired with a handheld Raman spectrometer using a 785 nm laser. This system demonstrates high selectivity and sensitivity, with limits of detection (LODs) of 3.58 nM for EC and 4.83 nM for SERS, enabling the effective quantification of PSA in human serum samples, suggesting its potential as an alternative tool for early cancer diagnostics.

Liu et al. synthesized nonmetallic plasmonic MoS₂ nanosheets via a hydrothermal top-down method to enhance the electrochemiluminescence (ECL) signal of sulfur-doped boron nitride quantum dots (S–BN QDs) [144]. However, close or far spacing between ECL luminophores and plasmonic NPs was observed to reduce the ECL intensity of both the nano-luminophore and the plasmonic NPs. This innovative DNA sensor achieved high detection efficiency for the hepatitis C virus gene, with a detection range of 0.5 pM to 1 nM and an LOD of 0.17 pM. Nor et al. developed a rapid and highly sensitive SPR detection platform for the SARS-CoV-2 spike protein (S protein) by utilizing various support layers, including MoS₂–COOH, 3-mercaptopropionic acid (3-MPA), and self-assembled monolayers of 11-mercaptoundecanoic acid (11-MUA) [145]. Among these, the SPR setup incorporating the MoS₂–COOH layer demonstrated the highest sensitivity of 203.55°/RIU, significantly outperforming 11-MUA (89.89°/RIU) and 3-MPA (108.90°/RIU). The exceptional sensitivity of the MoS₂–COOH layer can be attributed to a combination of factors. First, MoS₂–COOH exhibits high chemical stability and strong resistance to oxidation, ensuring consistent and reliable interactions at the sensor surface. Additionally, MoS₂–COOH has a large surface area, which enhances the immobilization of biomolecules, thus strengthening the binding interactions with the SARS-CoV-2 spike protein. Furthermore, the presence of carboxylic acid functional groups in MoS₂–COOH improves the bioaffinity of the sensor surface, enabling stronger covalent bonding with immobilized ligands. Moreover, MoS₂’s unique optical properties amplify the surface plasmon resonance effect, leading to more pronounced shifts in resonance angle when the target binds to the sensor surface. The specialized architecture of the MoS₂–COOH layer further optimizes the light coupling and plasmonic effects, thereby enhancing the overall detection capability. Due to these combined properties, the MoS₂–COOH layer considerably outperforms traditional thiol-based self-assembled monolayers, making it an ideal candidate for developing highly sensitive SPR biosensors for virus detection. All configurations exhibited outstanding sensitivity, excellent linearity, and low detection limits in the ng/mL range, establishing a rapid, noninvasive, and ultrasensitive SPR detection platform for detecting viral pathogens at low concentrations.

4.2.2. MoS₂–Plasmonic Hybrid Platforms for Bioimaging

MoS₂–plasmonic hybrid platforms are extensively used in bioimaging applications, facilitating the investigation of cellular and tissue properties, as well as the real-time monitoring of intracellular NP and drug trafficking. Although bioimaging encompasses various imaging modalities, such as light [155,156], X-rays [157,158], electron microscopy [159], positron emission [160,161], and magnetic resonance [162,163], this review will focus only on bioimaging studies using optical microscopy.

Maji et al. [146] developed a hybrid structure that combines gold nanobipyramids (AuNBPs) with a MoS₂ semiconductor layer, creating a multifunctional tool for anticancer therapy and two-photon bioimaging. This hybrid material showed considerably improved LSPR properties when excited owing to its anisotropic structure and the high electron density of MoS₂. As a result, there was an increased in situ photogeneration of reactive oxygen species (ROS), including singlet oxygen (¹O₂) and hydroxyl radicals (•OH) (Figure 5A). The combined effects of enhanced photothermal conversion and ROS generation led to markedly improved anticancer efficacy of the AuNBPs@MoS₂ hybrid. An increase in optical absorbance, leading to enhanced photothermal activity (from 25 °C to 60.3 °C), was achieved owing to the strong electronic connection and plasmonic coupling between the AuNPs and MoS₂ nanosheets. Importantly, the AuNBPs@MoS₂ hybrid demonstrated peroxidase-like nanozyme activity under acidic conditions, with its performance doubling in the presence of NIR light, which promoted additional ROS generation through plasmonic effects. The subcellular localization of AuNBPs@MoS₂ was confirmed through in vitro cellular uptake studies in HeLa cells, revealing clear two-photon luminescence (TPL) imaging. These catalytic and photothermal properties were effectively used to achieve high therapeutic efficacy against HeLa cancer cells, resulting in cell viability of 13.2%, highlighting the potential of sequential and combinatorial therapy approaches. The successful internalization of AuNBPs@MoS₂ in cancer cells, validated through TPL imaging, facilitated concurrent anticancer therapies via catalytic and photothermal mechanisms (Figure 5B–D).

Xu et al. [147] developed a composite nanoprobe (Ag@MoS₂) for in situ fluorescence imaging and quantitative analysis of intracellular adenosine triphosphate (ATP) levels in HeLa cells using fluorescence spectrometry and inductively coupled plasma mass spectrometry (ICP–MS). This probe was created by adsorbing DNA–Ag nanoclusters (AgNCs) onto MoS₂ nanosheets, with the DNA–AgNCs being synthesized using an ATP aptamer as a template. Initially, the fluorescence of the DNA–AgNCs was quenched by MoS₂. Upon incubation with cells, intracellular ATP recognized the aptamer sequence, resulting in the detachment of the DNA–AgNCs from the MoS₂ nanosheets and restoring fluorescence. Here, AgNCs acted as both a fluorescent label for imaging and an elemental tag for quantifying intracellular ATP by detecting ¹⁰⁷Ag via ICP–MS. The measured ATP concentration in HeLa cells using this method was 24.6 ± 1.7 nM, closely aligning with the ATP test kit result of 20.4 ± 0.8 nM.

4.2.3. MoS₂–Plasmonic Hybrid Platforms for Phototherapy

Phototherapy, encompassing PTT and photodynamic therapy (PDT), is gaining prominence as an alternative to traditional cancer treatments [164,165]. Unlike conventional therapies, phototherapy offers unique advantages: accurate control over irradiation parameters (location, duration, and intensity). This section explores the use of MoS₂–plasmonic hybrid platforms in both PTT and PDT.

In PTT, a phototransducer material efficiently absorbs light, especially in the NIR range, and converts it into heat. This localized thermal ablation targets cancerous cells or tissues [166,167]. NIR light is particularly advantageous for PTT owing to its deep tissue penetration, low absorption by biological tissues, and noninvasive nature, making PTT a promising therapeutic option for treating tumors [165,168]. Various organic NIR-responsive dyes and nanomaterials have been investigated as potential phototransducer materials.

Among nanomaterials, MoS₂ stands out for its unique properties: catalytic activity, direct bandgap, broad spectral response, and high photothermal conversion efficiency (PCE). These attributes make it a key material in photocatalysis research [153,169]. Notably, MoS₂ has gained recognition as a biocompatible nanomaterial with exceptional light-to-heat conversion capabilities. While pure MoS₂ exhibits promising biocompatibility, its catalytic and antibacterial performance may be limited. To address this, researchers have explored the combination of MoS₂ with plasmonic metal NPs, showing great promise for enhancing the efficacy of phototherapy [170]. This performance enhancement can be primarily attributed to the LSPR phenomenon, which is exhibited by Au plasmonic NPs. This phenomenon amplifies local electromagnetic fields and improves light absorption. The interaction between AuNPs and MoS₂ generates high-energy “hot electrons”, which are effectively transferred to the MoS₂ nanomaterial, injecting additional energy into the system. Moreover, MoS₂ possesses inherent piezoelectric properties that enable it to generate an electric field when subjected to mechanical strain, further facilitating the separation and migration of charge carriers. The synergy between LSPR and piezophototronics considerably reduces the recombination rates of electron–hole pairs, which, in turn, improves the catalytic activity of MoS₂. This synergy not only enhances charge dynamics and light absorption but also results in more efficient PTT and PDT, yielding improved outcomes in various applications, such as cancer treatment and microbial disinfection.

Liu et al. engineered a Bi/MoS₂ heterojunction complex in a fibrin gel, which demonstrated antibacterial efficiencies of 99.2% and 99.7% against S. aureus and E. coli, respectively, under 808 nm NIR irradiation, surpassing the MoS₂-only group [148]. This enhanced antibacterial effect stems from the synergistic action of photothermal conversion and ROS production upon light exposure. This improvement in antibacterial efficacy is mainly due to the LSPR phenomenon exhibited by the Bi NPs. Under 808 nm NIR light, the electrons on the surface of the Bi NPs resonate, generating an amplified electromagnetic field. This resonance leads to enhanced light absorption, resulting in localized heating that considerably improves the photothermal conversion efficiency, surpassing that of MoS₂ alone. In addition, the inclusion of Bi NPs improves charge separation and transport within the heterojunction, which is crucial for ROS generation under NIR irradiation. The synergistic effects of intense localized heating generated by the Bi NPs and ROS produced by MoS₂ disrupt bacterial membranes and induce oxidative damage. This dual mechanism explains the high antibacterial activities of 99.2% and 99.7% against S. aureus and E. coli, respectively. These findings highlight the potential of the Bi/MoS₂ heterojunction complex as a highly effective antimicrobial agent, particularly for wound healing applications. Furthermore, the photothermal effect induced protein denaturation, effectively eradicating bacteria in both in vitro and in vivo settings. In vivo animal studies corroborated the bactericidal capabilities of the gel under light irradiation while simultaneously demonstrating its potential in promoting diabetic wound healing through the stimulation of collagen formation, re-epithelialization, and angiogenesis.

Wang et al. used an in situ growth technique to integrate Au NRs with MoS₂, synthesizing MoS₂@AuNRs (MA) NPs with an impressive PCE of 42.16% [149]. Subsequently, hydroxyapatite (HAP) and polydopamine (PDA) were self-assembled onto the MoS₂@AuNRs NPs (Figure 6A). These NPs exhibited substantial temperature increases, reaching 34.1 °C for MoS₂@AuNRs and 30 °C for MoS₂@AuNRs/HAP/PDA (MAHP) after 60 min of laser irradiation. These findings corroborate the potent NIR-dependent photothermal properties of MoS₂@AuNRs, with temperature increases directly proportional to NP concentration and exposure time. To evaluate the NIR and pH-responsive drug release performance of MAHP, 4 W/cm² NIR laser irradiation was applied after 4 h at pH 4.5 (Figure 6B). The release of the anticancer drug doxorubicin hydrochloride (DOX) was limited to 26.57% after 4 h and reached 49.95% after 10 h. This phenomenon is attributed to the heat generated by the MA NPs, which accelerates the dissociation of the weak electrostatic bond between MAHP and DOX. Notably, the MoS₂@AuNRs/HAP/PDA NPs exhibited a high DOX loading capacity of 80%, along with pH- and NIR-responsive drug release properties. This is facilitated by the structural breakdown of HAP in acidic conditions and the strong NIR response of MoS₂@AuNRs. In vitro cell viability assays demonstrated that MoS₂@AuNRs/HAP/PDA NPs effectively inhibited MCF-7 cells under NIR laser irradiation and acidic conditions (Figure 6C).

In PDT, a photosensitizer (PS) is used to generate ROS upon light exposure [171]. The PS transitions to an excited state, transferring energy to oxygen molecules in its vicinity, leading to ROS formation. These highly reactive species oxidize lipids, DNA, and proteins, ultimately causing cell death [172,173]. PDT offers minimally invasive treatment and effectively targets even small, hidden tumor cells.

Li et al. developed MoS₂–AuNRs–aptamer NPs capable of actively targeting lipopolysaccharides (LPS) on Gram-negative bacteria, enabling effective antimicrobial action against multidrug-resistant Pseudomonas aeruginosa (MRPA) in wound models [150]. These targeted NRs exhibited superior antimicrobial efficacy compared to nontargeted PTT, effectively eliminating MRPA bacteria through physical damage. The enhanced effectiveness of the MoS₂–AuNRs–aptamer is primarily attributed to its ability to actively target LPS on the MRPA surface. This targeted approach facilitates more efficient delivery of PTT directly to the bacterial cells, enabling localized heating and physical disruption of the bacterial structure under NIR irradiation. The aptamer’s specific binding to LPS facilitates NP accumulation at the infection site and considerably enhances thermal damage to the bacteria. As a result, the targeted approach acheives a more pronounced reduction in bacterial viability than nontargeted PTT, which lacks specificity and risks damaging surrounding healthy tissues without effectively targeting the bacteria. Furthermore, the use of targeted NPs substantially reduced M1 inflammatory macrophages, thereby promoting an improved wound healing environment.

Younis et al. combined MoS₂ and AuNRs to create a dual plasmonic PTT nanoagent, achieving a remarkable temperature increase of up to 60 °C with a PCE of 68.8% in 5 min under low-power NIR laser irradiation (0.2 W/cm²) [45]. This enhanced PCE and PTT efficacy were attributed to the synergistic plasmonic PTT (PPTT) effects of the dual plasmonic agents (MoS₂ and AuNRs), enabling the efficient release of electrostatically bound indocyanine green (ICG) for simultaneous PDT and PPTT. AuNRs exhibit strong LSPR, efficiently absorbing NIR light and converting it into heat, while MoS₂ contributes with its large surface area and NIR light absorption abilities, which aid in charge separation. The combination of these materials enhances light absorption and increases the overall photothermal conversion efficiency, resulting in a substantial temperature rise of up to 60 °C under low-power laser irradiation. This synergistic effect improves heat generation and promotes the efficient thermal release of electrostatically bound ICG, thereby activating PDT and PPTT simulatenously, ultimately delivering superior therapeutic outcomes in cancer treatment.

Yougbare et al. synthesized light-responsive hybrids that have attracted considerable attention in the biomedical field for antibacterial applications [151]. Specifically, they developed metallic molybdenum disulfide nanosheets (1T-MoS₂ NSs) activated by visible light and combined them with plasmonic AuNRs exhibiting absorption at a wavelength of 808 nm. The AuNRs were successfully prepared via electrostatic adsorption onto 1T-MoS₂ NSs forming MoS₂@AuNRs for potential phototherapy applications. The authors demonstrated that the solution temperature MoS₂@AuNR increased from 25 °C to 66.7 °C within 10 min of NIR laser irradiation at 808 nm, emphasizing the effectiveness of the photothermal effect. In addition, the MoS₂@AuNR hybrids generated RSO under visible light irradiation, contributing to their photodynamic effects. The antibacterial efficacy of MoS₂@AuNRs against E. coli was confirmed using agar plate count assays, illustrating their potential use in phototherapy. Notably, the combination of PTT and PDT provided by the MoS₂@AuNR hybrids demonstrated greater antibacterial activity compared with individual therapy. This remarkable synergistic effect highlights the innovative potential of light-activated MoS₂@AuNR hybrids to combat bacterial infections.

Liu et al. developed a novel PTT/PDT antitumor theranostic nanoplatform based on chlorin e6 (Ce6)-loaded PEG–MoS₂–AuNP hybrids. These hybrids substantially enhanced PTT efficacy for cancer treatment under 808 nm laser irradiation, attributed to their unique material properties and synergistic mechanisms. The MoS₂ nanomaterial provides strong NIR absorption, while the AuNPs enhance photothermal conversion through SPR. Together, these components generate substantial heat under laser exposure, achieving temperatures sufficient to induce thermal damage to cancer cells. Additionally, the hyperthermic environment promotes the release of the Ce6 photosensitizer, which activates PDT by generating ROS upon irradiation. This dual-action approach directly destroys tumor cells via thermal effects and enhances PDT efficacy, creating a synergistic effect that markedly improves therapeutic outcomes against tumors. Furthermore, Ce6 release from the hybrids produced strong NIR fluorescence signals, initiating the PDT effect for antitumor therapy. Notably, PTT effectively triggered both Ce6 release and ROS generation, resulting in a synergistic PTT–PDT effect that significantly improved cancer treatment efficacy [152].

Wei et al. developed an artificial nanozyme, Fe₃O₄@MoS₂–Ag, using a two-step hydrothermal method involving the in situ growth of AgNPs [153]. This nanozyme exhibited remarkable antibacterial activity against E. coli, achieving approximately 69.4% inhibition through the generation of ROS and the release of silver ion (Ag⁺) ions. Notably, its disinfection efficacy was further enhanced by the NIR photothermal properties of Fe₃O₄@MoS₂–Ag, reaching nearly 100% inhibition. The antibacterial mechanism relies on the synergistic effects of photothermal heating, peroxidase-like activity, and Ag⁺ ions release. The Fe₃O₄@MoS₂–Ag nanozyme exhibits peroxidase-like activity and catalyzes hydrogen peroxide conversion into ROSs—such as hydroxyl radicals—that effectively damage bacterial membranes. Concurrently, Ag⁺ release disrupts bacterial cellular functions by permeating membranes and interfering with vital processes. Additionally, the nanozyme’s photothermal properties allow it to absorb NIR light, generating localized heat that enhances ROS activity and promotes Ag⁺ release. This combination of mechanisms—where heat increases membrane permeability and ROS and Ag⁺ ions exert their antibacterial effects—results in considerably enhanced antibacterial efficacy, demonstrating the effective synergy of these three components in combating bacterial infections. The defect-rich rough MoS₂ surface facilitates bacterial capture, enabling the accurate and rapid action of ^•OH and Ag⁺ on the E. coli membrane, supported by local hyperthermia. This approach demonstrated broad-spectrum antibacterial efficacy against Gram-positive and Gram-negative bacteria, fungal pathogens, and drug-resistant strains.

Rodriguez-da-Silva et al. synthesized MoS₂ NFs through a hydrothermal method and used them as substrates for the deposition of small spherical monometallic Au or bimetallic AuAg NPs [154]. These hybrid nanostructures are novel photothermal-assisted catalysts, exhibiting enhanced catalytic efficiency under NIR laser irradiation. The improved catalytic performance results from the synergistic effect of combining MoS₂ NFs with either bimetallic AuAg or monometallic AuNPs. This combination facilitates electron transfer during the reduction of 4-nitrophenol to 4-aminophenol. MoS₂ serves as a 2D platform that absorbs light energy and converts it into thermal energy, thereby enhancing catalytic activity. The alloyed AuAg NPs increase electron density at the gold active sites, with silver donating electron density to adjacent gold atoms, thus increasing their reactivity. Additionally, MoS₂’s strong NIR light absorption enables efficient conversion of this energy into heat, which accelerates reaction kinetics. The enhanced kinetics creates a cooperative catalytic mechanism where MoS₂ provides photothermal effects and acts as a substrate, while the metal NPs engage in electron transfer and reduction reactions. This synergistic interaction substantially enhances the catalytic process, outperforming the independent performance of each component. Notably, the synthesized hybrid NPs integrate these critical factors, considerably accelerating the reduction rate of 4-nitrophenol to 4-aminophenol.

5. Challenges and Future Perspectives

MoS₂–plasmonic hybrid platforms have demonstrated considerable potential in various biological applications, including biosensing, bioimaging, and phototherapy [33,42,87,174]. However, to fully realize their clinical potential, several challenges must be addressed, including synthesis reproducibility, toxicity, stability under physiological conditions, targeted delivery, and scalable manufacturing.

The inherent reactivity of MoS₂ can lead to degradation or alteration of its optical and electrical properties over time, potentially compromising the functionality of the hybrid system. To mitigate this, advanced encapsulation and passivation techniques must be developed to protect MoS₂ and maintain the overall stability of the hybrid structure.

Future research should focus on developing robust encapsulation strategies, such as employing biocompatible polymers or inorganic coatings like silica or alumina, to shield MoS₂ from degradation while preserving its optical and electrical properties. in addition, in vivo studies are essential to assess the long-term effects of these encapsulation methods on the stability and performance of hybrid platforms under dynamic physiological conditions.

Improving biocompatibility and in vivo performance also necessitates thorough toxicological studies to ensure minimal adverse effects on healthy tissues. Concurrently, designing and synthesizing targeted delivery systems, such as ligand-conjugated NPs or aptamer-functionalized platforms, are crucial for ensuring the specific delivery of hybrids to diseased tissues while minimizing off-target accumulation and side effects.

Synthesis reproducibility is another notable challenge. Methods to consistently produce hybrid structures with uniform size, shape, and composition—such as microfluidic or continuous flow techniques—are essential for clinical translation. Investigating the effects of synthesis parameters, such as temperature, reactant concentration, and reaction time, on the physicochemical properties and biological performance of the platforms is necessary. Addressing variability in synthesis is critical to ensuring consistent performance and safety.

Navigating the regulatory landscape for clinical translation is also vital. The complexity of MoS₂–plasmonic hybrids may pose challenges in meeting regulatory requirements, potentially delaying approval and clinical use. Clear guidelines are needed to facilitate the translation of these innovative therapies into clinical practice.

To fully exploit the potential of MoS₂–plasmonic hybrid platforms, enhancing their sensitivity and specificity is crucial. Research should focus on optimizing the size, morphology, and composition of plasmonic components to maximize optical signal enhancement, thereby achieving enhanced detection and imaging capabilities.

Finally, practical devices for real-life applications must be developed. Efforts should be directed toward integrating MoS₂–plasmonic hybrid platforms into user-friendly, portable biosensors or point-of-care devices for real-time diagnostics and personalized medicine.

Addressing these challenges requires a multidisciplinary approach involving close collaboration among materials scientists, engineers, biologists, and clinicians. With continued research and development, MoS₂–plasmonic hybrid platforms can revolutionize diagnostics, therapeutics, and personalized healthcare.

6. Conclusions

MoS₂–plasmonic hybrid platforms are revolutionizing nanomedicine by merging the extraordinary optical, electrical, and catalytic properties of MoS₂ with the signal-enhancing capabilities of plasmonic materials. These hybrids have emerged as exceptional tools for biosensing, bioimaging, and phototherapy, offering accurate and minimally invasive solutions for diagnostics and treatments. The synergistic interactions between MoS₂ and plasmonic NPs enable advancements in sensitivity, specificity, and therapeutic efficacy, making them highly versatile for a wide range of biomedical applications.

Although MoS₂–plasmonic hybrid platforms have demonstrated potential in various biological applications, challenges such as synthesis reproducibility, toxicity, stability under physiological conditions, targeted delivery, and scalable manufacturing remain. Advances in synthesis techniques and the fostering of interdisciplinary collaboration will play a crucial role in overcoming these limitations. With sustained innovation, MoS₂–plasmonic hybrid platforms are poised to revolutionize biomedical science by providing next-generation solutions for complex health challenges. These platforms have the potential to redefine diagnostic and therapeutic paradigms, paving the way for groundbreaking advancements in personalized healthcare.