Cancer is a major public health concern requiring high-precision therapy with minimal side effects. According to GLOBOCAN statistics, the incidence of cancer is projected to surpass 19 million, with a mortality rate of up to 10 million [1]. The first-line cancer treatment, including the combination of treatments, such as surgery (removing tumor mass), chemotherapy, and radiation therapy, demonstrated cancer inhibition and provided relief [2,3]. However, these treatments exhibit potential limitations, including tumor recurrence, unnecessarily high drug dose rates, low targeting ability, and other associated side-effects [4], [5], [6], [7], [8]. Alternative approaches, such as photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), and piezocatalytic therapy (PZT), have gained significant attention worldwide because of ability to solve aforementioned limitations [9], [10], [11]. Most notably, the application of such alternative therapeutic approaches has resulted in a reduction in their systemic toxicities through selective targeting, and the ability to manipulate the tumor microenvironment (TME). Additionally, combining any of these therapeutic modules has been observed to have a synergistic effect, leading to a significant increase in therapeutic efficiency.

In recent decades, the integration of nanotechnology-based drug delivery systems and the application of multiple anticancer agents has represented a promising approach to revolutionize cancer therapy [12], [13], [14]. Based on the available evidence, nanomaterials have been found to offer several advantages, such as 1) enhancement of the solubility and stability of chemotherapeutic drugs, 2) extension of the blood circulation time of drugs, leading to increased cellular uptake efficiency, 3) promotion of non-invasiveness, and 4) provision of specific targeting ability [15], [16], [17], [18]. Several nanoplatforms are based on polymers [19], carbon dots [20], liposomes [21], metallic nanoparticles [22], and transition metal dichalcogenide (TMD)-based materials. In the TMD family, molybdenum disulfide (MoS2) has been observed to exhibit a distinct therapeutic, and possess relatively low toxicity, rendering it a promising candidate for further investigation into biomedical applications [11,23]. At the atomic scale, the transition from bulk crystal to monolayer MoS2 results in tunable bandgaps that significantly affect its optical and physicochemical properties. Intriguingly, by controlling the number of layers, the bandgap can be adjusted, and MoS2 can be engineered to exhibit specific properties that make it suitable for various biomedical applications [24], [25], [26]. The development of nanomedicines using MoS2 nanostructures offers several advantages. First, MoS2 exhibits distinctive optical semiconducting properties [24], making it an attractive candidate for drug delivery [27] and biosensing applications [23]. Second, the simple synthesis procedures enable the production of MoS2 nanostructures in large quantities, facilitating their wide adoption in biomedical research. Third, MoS2 has structural defects, including point defects, grain boundaries, and edges, which facilitate easy surface alteration and functionalization, further influencing the chemical, electrical, and optical properties necessary for cancer therapy [23,28]. Nevertheless, MoS2 is well known for its outstanding chemical, photochemical, and thermal stability [29], [30], [31]. Most importantly, MoS2 has various morphologies such as nanosheets [32], nanoflake [33], nanoflower [34], and quantum dots (QDs) [35], making it suitable for shape-dependent cancer therapy applications [36], [37], [38]. Based on our observations, the structural forms of nanosheets/nanoflakes, nanoflowers, and QDs have been widely used in various applications. Each of these forms demonstrates a unique set of features with several advantages and disadvantages. For instance, the large active surface area of MoS2 presents a promising opportunity for multi-drug loading and targeted ligand attachment, while the flower-like structure exhibits high drug encapsulation/entrapment efficiency, and minimum leakage. It is worth mentioning that both nanosheets and nanoflowers exhibit a size distribution within the range 100–500 nm, which may impose certain constraints on their potential to facilitate efficient drug delivery via the bloodstream. In this regard, QDs are potential alternatives owing to their small size range (1–10 nm). Thus, the selection of an appropriate structural form depends on the specific requirements of the intended application, and careful evaluation of the advantages and limitations of each form is essential for optimal outcomes.

In this review, we comprehensively elucidate the latest developments in MoS2-based nanostructures for cancer therapy, with a primary emphasis on Chemo, immunotherapy (Immuno), RT, PTT, PDT, CDT, PZT, and their synergistic combinations. According to Scopus search, over 100 articles on MoS2-based drug delivery platforms were published in the last five years; however, there is a lack of comprehensive review articles. Most importantly, the utilization of the catalytic properties of MoS2 in cancer therapy has been overlooked. Our review aims to bridge this gap by emphasizing structure-mediated drug loading/release and the therapeutic roles of MoS2-based nanoplatforms. Subsequently, an exhaustive attempt was made to collate interesting research findings and critically emphasize authoritative viewpoints, followed by a brief commentary on the future outlook of clinical translations and associated ethical and legal issues. This review will inspire novice and expert researchers to develop next-generation MoS2-based functional nanomedicines for cancer therapy and other biomedical applications.