95].

Another significant challenge in the field of nanomedicine is the development of advanced theranostic platforms with both therapeutic and diagnostic capabilities. In this regard, 3D porous MoS₂ nanoflowers were synthesized, then loaded with doxorubicin and coated with PEG-PEI (conjugated with LIM Kinase 2 protein (LMP) nucleolar translocation signal peptide). LMP peptide improved the nanomaterials’ nuclear targetability in cancer cells. Thus, these materials were able to specifically target the cancer cells and could exert potent anticancer effects both in vitro (4T1 cells) and in vivo (4T1 tumor bearing mice model) through pH-responsive/NIR-enhanced doxorubicin delivery into the tumor cells, NIR-induced photothermal effects along with ROS generation due to POD-like activity of MoS₂ nanoflowers. Furthermore, the excellent photoacoustic properties of these materials allowed for real-time tracking post-intravenous in the 4T1 tumor bearing mice models ^[60][96]. A smart hybrid NZ based on MoS₂-coated bipyramidal gold nanostructure was developed for anticancer therapy and two-photon bioimaging. This hybrid nanomaterial produced considerable ROS due to the POD-like activity of MoS₂, which was augmented further by irradiation with 808 nm NIR laser due to localized plasmonic effects. Such synergistic ROS generation exerted significant anticancer effects in HeLa cells, as confirmed by two-photon luminescence imaging ^[61][97].

Apart from the applications listed above, TMDC NZs, particularly those with CAT/SOD-like activity, have also been used as antioxidant materials to provide cytoprotective effects and treat inflammatory diseases/conditions such as osteoarthritis and neurodegeneration ^[62][63][64][98,99,100]. For example, MoS₂ nanosheets with CAT/SOD-like activity were synthesized those were able to quench and reduce the levels of free radicals like nitric oxide (^●NO), ^●OH, and nitrogen-centered free radicals (^●DPPH). Furthermore, treating H₂O₂-exposed A549 cells with these nanomaterials dramatically reduced oxidative stress ^[63][99]. Fullerene-like MoS₂ (F-MoS₂) is another interesting TMDC-NZs with CAT-/SOD-like activities under physiological settings that appropriate it for using for the non-surgical treatment of osteoarthritis. F-MoS₂ was able to catalyze ^●O₂^– into H₂O₂ and then produce water and O₂. Interestingly F-MoS₂ was used to protect HUVEC cells from oxidative stress induced by H₂O₂. Besides, F-MoS₂, when coupled with hyaluronic acid (HA), could reduce the excess of ROS and prevent the depolymerization of HA in artificial synovial fluid ^[64][100]. TMDC NZ with CAT-/SOD-like activity was used to mitigate the pathology of Alzheimer’s disease by targeting neuronal mitochondria with (3-carboxypropyl)triphenyl-phosphonium bromide-conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(PEG)-2000]-functionalized MoS₂ QDs. When tested in vitro in murine-derived microglia BV2 cells, this nano-formulation dramatically decreased oxidative stress, downregulated pro-inflammatory cytokines, and elevated anti-inflammatory cytokines. Furthermore, in vitro (in BV2 cells) and in vivo (in an Alzheimer’s disease mouse model) tests revealed that these nanomaterials were able to reduce amyloid-beta (Aβ) aggregation-mediated neurotoxicity and eliminate Aβ aggregates. These were attributed to switching microglial polarization from pro-inflammatory M1 to anti-inflammatory M2, presenting a novel pathway to mitigate Alzheimer’s disease pathology ^[28][101].

Applications	TMDCs Material	Activity Mimics	Targeting Molecule (if Any)	Therapeutic Mechanism	Therapeutic Mediators	Light Characteristics (if Involved)	Activity Assessed Against		In Vivo Evaluation	Ref.
							Microbial Cells	Mammalian Cells
Disinfection and wound healing	MoS2/rGO	POD-like, OD-like, CAT-like		ROS-mediated	H2O2	Xenon lamp (100 mW/cm2)	Chloramphenicol-resistant E. coli and S. aureus		S. aureus-infected full-skin defect mice models	[50][52]
	Fe3O4@MoS2-Ag	POD-like		Ag+ ion-mediated toxicity, ROS-mediated, PTT	H2O2, Ag+ ions	NIR (808 nm, 1 W/cm2)	E. coli			[43][102	[19]
	]	H2O2	Au NRs-anchored MoS2/C	POD-like		Colorimetric	TMB	10–200 μM	1.82 μM
	citraconic anhydride modified PEI-MoS2	POD-like		Disruption of surface charge, ROS-mediated	H2O2, 2-nitrobenzaldehyde	UV light (365 nm)	E. coli and S. aureus		E. coli and S. aureus-infected full-skin defect mice models	Cancer cells	[54][89][20]
	H2O2	MoS2/Ppy	POD-like		Colorimetric	TMB	50–2000 μM	45 μM			[
	WS2 QDs-Van@lipo	POD-like, OD-like		ROS-mediated, PTT, Chemotherapy	H2O2, vancomycine	NIR (808 nm, 1 W/cm2)	E. coli and Mu50 (vancomycin-intermediate	21	]
	S. aureus	strain)		Mice models with Mu50-infected abscess	[	55	]	[	60	]	Glucose	MoS2	POD-like	GOx	Colorimetric	TMB	5–150 μM
	Cu NW-supported MoS2 NS	POD-like		1.2 μM		Human serum	ROS-mediated, PTT	H2O2	NIR (808 nm, 1 W/cm2)[22	E. coli and S. aureus]
		MRSA-infected full-skin defect mice models	[	36	]	[	51	]	Glucose	MoS2 QDs	POD-like	GOx	Fluorometric		10–1500 μM	5.16 μM		Fetal bovine serum	[
N-doped MoS2, N-doped WS2	POD-like		ROS-mediated	H2O2		23	]
Ampicillin resistant	E. coli	and	B. subtilis		Ampicillin resistant	E. coli	-infected full-skin defect mice models	[	65][42]	Glucose	PTCA-MoS2	POD-like	GOx	Colorimetric	TMB	20–800 µM	18.3 μM	2 months (at 4 °C)
Lysozyme exfoliated MoS2 NSs	POD-like		ROS-mediated	H2O2		Human serum	Ampicillin-resistant E. coli and B. subtilis			[53][88][24]
Glucose	MoS2-MIL-101(Fe)	POD-like	GOx	Colorimetric	TMB	0.01−15 μM
PEG-MoS2 NFs	POD-like		ROS-mediated, Photothermal therapy (PTT)	H2O2	NIR (808 nm, 1 W/cm2)	Ampicillin-resistant	0.01 μM	1 month	Human serum	E. coli and B. subtilis		Ampicillin resistant E. coli-infected full-skin defect mice models	[56[25]
]	[	90	]	Glucose	MoS2@MgFe2O4	POD-like	GOx	Colorimetric	TMB, ABTS	5–200 μM
CMSF-MoSe2 NSs	POD-like		ROS-mediated	H2O	2 μM	1 month	Human serum	2[26		E. coli and B. subtilis]
	E. coli	-infected full-skin defect mice models	[	52	]	[	87	]	Glucose	Cysteine- MoS2 NF	POD-like	GOx	Colorimetric	ABTS	50–1000 μM	33.51 μM		Human serum	[27]
Glucose	Dextran-MoSe
Anticancer therapy	Glucose responsive, TMZ-loaded chitosan-MoS2	POD-like		ROS-mediated, GSH depletion, hypoxia induced TPZ activation	H2O2 and TPZ			A549 cells	A549 tumor-bearing mice models	[59][95]	2	POD-like	GOx	Colorimetric	TMB	40–400 µM	28 µM	10 days	Human serum	[28]
	AuNBPs@MoS2	POD-like		ROS-mediated, PTT	H2O2	NIR laser (808 nm, 2.0 W/cm2)		HeLa cells		[61][97]	Glucose	Chitosan-MoSe2	POD-like	GOx	Colorimetric	TMB	5–60 µM
	LNP-PEG-PEI coated, Dox loaded MoS2 NFs	POD-like	LNP nucleolar translocation signal peptide	ROS-mediated, CT, PTT, PDT	Dox	NIR laser (808 nm, 3.0 W/cm2)		0.71 μM	>1 month	Human serum	[29]
	4T1 cells	4T1 tumor-bearing mice models	[	60	]	[	96	]	Glucose	SDS–MoS2	POD-like	GOx	Colorimetric	TMB	5–500 μM	0.57 μM
MoSe	Human serum	2	[	30	]
/CoSe2@PEG	POD-like, CAT-like		ROS-mediated, GSH depletion, PTT	H2O2	NIR laser (808 nm, 1.0 W/cm2)		HepG2 cells	Tumor-bearing mice models	[58][94]	Glucose	AuNPs@MoS2 QD	POD-like	GOx	Colorimetric	TMB	20–400 μM
Cytoprotection	MoS2	0.068 μM	12 days	Human serum, tear and saliva	NS	[	31]
CAT-like, SOD-like, POD-like		Scavenging oxidative stress species			E. coli	and	S. aureus	A549 cells		[63][99]	Glucose	PVP-MoS2 NPs	POD-like	GOx	Colorimetric	TMB	1000–10,000 μM	320 μM
Neurodegeneration	Fetal bovine serum	[	32	]
TPP-MoS	2 QDs	CAT-like, SOD-like	TPP (mitochondrial targeting)	Scavenging oxidative stress species				BV-2 cells	Amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice	[28][101]	Glucose	WS2	POD-like	GOx	Colorimetric	TMB	5–300 μM	2.9 μM		Human serum	[33]
Osteoarthritis	Fullerene-like MoSGlucose	WS2 NS + Ag NCs	POD-like	GOx	Chemiluminescence	Sodium bicarbonate	0.03–20 μM	0.0013 μM		Human serum	[34]
Glucose	Hemin-WS2	POD-like	GOx	Colorimetric	TMB	5–200 µM	1.5 μM		Human serum	[35]
Glucose	WSe2	POD-like	GOx	Colorimetric	TMB	10–60 μM	10 μM			[36]
Glucose	VS2	POD-like	GOx	Colorimetric	TMB	5–250 µM	1.5 µM			[37]
Cholesterol	MoS2 NS	POD-like	ChOx	Colorimetric	TMB	2–200 μM	0.76 μM		Human serum	[38]
2	CAT-like, SOD-like		Scavenging oxidative stress species				HUVECs		[	64][100]	Cholesterol	MoS2 nanoribbons–AuNPs	POD-like	ChOx	Colorimetric	TMB	40–1000 μM	15 μM		Human serum	[39]
Cholesterol	Oxidized GSH-modified MoS2 NSs	POD-like	ChOx	Colorimetric	TMB	5.36–800 μM	5.36 μM		Mouse serum	[40]
GSH	WS2 NSs	POD-like		Colorimetric	TMB	0.1–10 nM	0.061 nm		Human serum	[41]
Uric acid	MoS2 NFs	POD-like	Uricase	Colorimetric	TMB	0.5–100 μM	0.3 μM		Human serum	[42]
Xanthine	MoSe2	POD-like	XOx	Colorimetric	TMB	10–320 µM	1.964 μM		Human serum	[43]
Cysteine	MoS2 QDs-Ag NPs (stimulated by Hg (II) ion)	OD-like		Colorimetric	TMB	1–100 μM	0.82 μM	1 month	Human serum	[44]
CEA	Aptamer/MoS2 NSs	POD-like		Colorimetric	TMB	50–1000 ng/mL	50 ng/mL		Human serum	[45]
Lipase	MoS2 NPs	POD-like		Colorimetric	TMB	5–200 nM	4.8 nM			[46]
Mucin 1	Aptamer-MoS2/PtCu	OD-like	NA	Colorimetric	TMB	NA	300 cells of MCF-7		MCF-7, A549, HEK293, and HepG2	[47]

The annual increase in the cases of bacterial infections is one of the most challenging aspects of the global public health and safety ^[48][84]. In particular, an alarming rise in bacterial drug resistance—as a result of uncontrolled use of antibiotics—has heightened concerns in this context ^[49][85]. Significant efforts are being made to overcome this challenge through the development of novel antibacterial agents with greater efficacy and specificity than conventional antibiotics. Recently, a new type of antibacterial therapy with broadband antimicrobial capability, known as nanozyme-mediated antibacterial therapy (NABT), has been introduced. It entails the use of NZs, including TMDC-based, with POD-/OD-like enzymatic activities to regenerate ROS, which then exerts antibacterial effects via oxidation of the bacterial membrane’s polysaccharides, proteins, and lipids ^[50][52].

The antibacterial activity of TMDC NZs, along with their relatively biocompatible nature, may be advantageous during the wound healing process. Bacterial infections have already been shown to delay healing by increasing inflammatory responses at the wound site ^[51][86]. As a result, using appropriate antibacterial agents could help to restore and balance the accurate healing microenvironment and avoid any delays. MoSe₂ nanosheets/carboxyl-modified silk fibroin based wound dressing exerted considerable antibacterial effects on Escherichia coli and Bacillus subtilis due to their POD-like activity. The studies were conducted both in vitro and in vivo in E. coli-infected full-skin defect mice model in the presence of low amounts of H₂O₂ ^[52][87]. Another study used lysozyme, an enzyme capable of hydrolyzing bacterial cell wall peptidoglycan, as an exfoliating agent to generate MoS₂ nanosheets. These nanomaterials demonstrated enhanced antibacterial activity against ampicillin-resistant E. coli and B. subtilis, which was attributed synergistically to the antibacterial activity of lysozyme and the POD-like activity of MoS₂ nanosheets ^[53][88].

Another intriguing study was conducted by Niu and his colleagues, who used a combination of citraconic anhydride-modified polyethyleneimine (PEI)-MoS₂ nanosheets and a photoacid generator molecule, 2-nitrobenzaldehyde (2-NBA). When 2-NBA was exposed to 365 nm light, the pH of the solution decreased, which activated the POD-like activity of the NZs to produce ROS and impart antibacterial effects. Furthermore, the irradiation time changed the charge of the nanomaterial from negative to positive, thanks to the photoreactive characteristics of citraconic anhydride, allowing Gram selectivity for the developed antimicrobial system ^[54][89].

Multimodal therapy is usually considered to be more efficient and effective at imparting antibacterial effects. NZs were combined with photothermal and chemotherapy in a study by encapsulating WS₂ quantum dots (WS₂ QDs) and vancomycin in a thermal-sensitive liposome. The use of WS₂ QDs benefited in two ways: (i) their POD-like activity allowed the generation of ROS and (ii) their photothermal property resulted in heat generation (via 808 nm NIR laser irradiation), causing liposomal rupturing at the targeted site, resulting in a reduction in drug doses required. This anti-biofilm agent demonstrated excellent anti-biofilm activity, eradicating both E. coli and Mu50 (vancomycin-intermediate Staphylococcus aureus strain) both in vitro and in vivo ^[55][60]. Owing to POD-like activity and photothermal properties, PEG-functionalized MoS₂ nanoflowers imparted an efficient antimicrobial effect and improved wound healing rate in ampicillin-resistant E. coli-infected full-skin defect mice models ^[56][90]. Another study used mesoporous ruthenium nanoparticle that was loaded and capped with ascorbic acid prodrug and hyaluronic acid, respectively. Ciprofloxacin-coated MoS₂ nanosheets were further bound to the outer surface of the nanocomposite. Post-administration, hyaluronidase enzyme (produced by bacteria) would reduce the hyaluronic acid capping degradation and release of ascorbic acid and MoS₂ at the infected wound site. Ascorbic acid/MoS₂-mediated reactive radical generation, and ruthenium nanoparticles-mediated photothermal therapy, could synergistically eliminate multidrug-resistant bacterial strains in vitro. Furthermore, this therapeutic agent demonstrated promising efficacy in S. aureus-infected mice models (tested for biofilm dispersion inhibition) and S. aureus and Pseudomonas aeruginosa infected mice models (tested for wound healing). On the other hand, Ciprofloxacin loading did not affect the antibacterial potency of these nanocomposites ^[18][91].

Cancer is one of the leading causes of death due to its late diagnosis and insufficient effects of currently available treatments (e.g., chemotherapy, radiation therapy, and surgical treatment) ^[29][92]. NZs, including those based on TMDC, have recently gained prominence in cancer treatment. NZ-mediated cancer therapy, like antibacterial systems, uses POD-/OD-like activities to generate ROS and cause cancer cells to die ^[57][93].

NZ-mediated cancer therapy is often limited by the lower availability of intra-tumoral H₂O₂. To address this challenge, recently, MoSe₂/CoSe₂@PEG nanosheets were synthesized. Using dissolved O₂ and photoexcited electrons, this system was able to produce H₂O₂ via a sequential single-electron transfer mechanism. Furthermore, this NZ system showed potent dual POD- and CAT-like activities, which ensured efficient generation of ^●OH and O₂, respectively. ^●OH caused mitochondrial damage, whereas O₂ alleviated hypoxia and served as a source of H₂O₂. The anticancer effects were amplified by the nanomaterial’s excellent photothermal characteristics, as well as redox disruptions (through intracellular GSH reduction). Besides, biodegradability and urinal/fecal elimination (within two weeks post-administration) are other notable features of this therapeutic system ^[58][94].

In another study, a glucose-responsive, H₂O₂ self-supplying nano-catalytic reactor was developed by self-assembly of GOx, tirapazamine (TPZ) and chitosan on the surface of MoS₂ nanosheets. The catalytic mechanisms involved in the cascade are as follows: (i) catalysis of intra-tumoral glucose by GOx (in the presence of O₂) to produce H₂O₂ and lower the pH; (ii) utilization of H₂O₂ by POD-like activity of MoS₂ nanosheets to produce ROS—to damage the cancer cells. Meanwhile, depletion of O₂ would activate TPZ, whereas MoS₂ could utilize GSH to disturb cellular redox balance, further amplifying the anticancer effects. This therapeutic agent demonstrated potent anticancer effects on A549 cells in vitro and A549 tumor-bearing mice models in vivo. In contrast, even at concentrations as high as 100 g/mL, no cytotoxicity was observed in normal human umbilical vein endothelial cells (HUVEC). Furthermore, under in vivo conditions, these nanomaterials did not accumulate in normal organs, but instead degraded and were cleared out of the body, indicating minimal toxicity to normal tissues ^[59][