Applications of nanozymes in the diagnosis and treatment of gastrointestinal malignancies

Table 1 Comparative analysis of natural enzymes and nanozymes

Feature	Natural enzymes	Nanozymes	GI oncology relevance	Ref.
Composition	Proteins or RNA	Metals, metal oxides, carbon, etc	Nanozymes possess a high density of active sites	[22]
Selectivity	High substrate specificity	Broad-spectrum/low specificity	Beneficial for multi-target TME modulation	[19]
Stability	Low (susceptible to protease, heat)	Extremely high (chemically robust)	Resists gastric acid and proteolytic enzymes in GI tract	[19]
Catalytic activity	High turnover rate (Kcat)	Tunable, pH/light/H2O2 responsive	Allows selective activation in acidic TME	[23]
Production cost	High (complex preparation/purification)	Low (facile chemical synthesis)	Enables large-scale clinical translate/screening	[24]
Multifunctionality	Single catalytic function	Integration with imaging/therapy	Facilitates theranostics (diagnosis + therapy)	[25]

TME: Tumor microenvironment; GI: Gastrointestinal.

Table 2 Applications of nanozymes in non-invasive diagnosis of gastrointestinal malignancies

Types of tumors	Nanozyme	Mimic activity	Mechanism and Function	Detecting substances	Sample	Ref.
Gastric cancer	Au@Pt NRs	Peroxidase	Integration of nanozyme catalysis, gold nanoparticle amplification, and catalytic hairpin amplification	miR-196b and miR-221	Serum	[15]
	Co-TA@Ag NPs(3-MPBA)	Peroxidase	Hydroxyl esterification reaction of D-alanine, D-proline, and 3-MPBA	D-alanine and D-proline	Stomach fluid and saliva	[18-20]
	MoS2	Horseradish peroxidase	Utilizing nanozymes, hybridization chain reaction, and enzyme-catalyzed amplification technology	miR-19b-3p	Healthy individuals and stage I & III gastric cancer patients	[16]
	PEI-CuFc	Peroxidase	Sensitivity in colorimetric detection; high-efficiency peroxidase-mimicking catalyst	D-amino acids and urease	Saliva	[21]
	Pt/Ti3C2Tx Mxene	Peroxidase and thermal performance	Colorimetric-photothermal dual-mode detection and oxidation of chromogenic substrates	D-amino acids	Saliva	[22]
	Fe3O4@Pt	Peroxidase	Integration of transition metal doping, noble metal loading, and nano-peroxidase-mediated signal amplification strategies	CA72-4	Serum	[17]
Colorectal cancer	CoPt3@HA	Peroxidase	Peroxidase activity catalyzed colorimetric reaction	Circulating cancer stem cells	Blood and stool	[23]

Table 3 Applications of nanozymes in the treatment of gastric malignancies

Type pathway	Nanozyme	Mimic activity	Function	Tumor model	Ref.
DNA-templated Ag@Pd alloy nanoclusters	Ag@Pd	Peroxidase	Exhibit high photothermal conversion efficiency, enhanced reactive oxygen species generation, improved permeability, and enhance nanocatalytic therapy	MKN-45 cells and mouse model	[42]
Drug delivery system based on nanomotors	MnO2-Au-mSiO2	Peroxidase	Effectively link nanomotors, enhance reactive oxygen species production, and activate the stimulator of interferon genes pathway	MFC cells and mouse models; gastric cancer organoid models	[54]
Nanocoordination polymers	Zn-Quer	Anti-inflammatory and antioxidant properties	Induce cytotoxicity, inhibit angiogenesis, and disrupt molecular pathways related to cell proliferation and invasiveness	MKN-45 cells and mouse model	[55]
P-selectin protein platelet membrane encapsulates SAZ and cisplatin	Cu	Peroxidase	Specifically target cancer cells within aggressive primary tumors and metastatic lymph nodes	MFC cells and mouse models	[64]

Zn-Quer: Zinc-quercetin.

Table 4 Applications of nanozymes in the treatment of colorectal malignancies

Nanozyme	Type pathway	Mimic activity	Function	Tumor model	Ref.
MnO2	Platelet-mimetic MnO2 nanozyme/AIEgen composite	Catalase	Relieve hypoxia in the tumor microenvironment and perform photodynamic therapy	CT-26 cells and mouse models	[48]
Ru38Pd34Ni28	Ru38Pd34Ni28 ultra-thin ternary metal nanosheets	Catalase and multi-enzyme-like anti-inflammatory activity	Clear reactive oxygen species and reactive nitrogen species; enhance photothermal conversion efficiency and antioxidant activity	CT-26 cells and mouse models	[49]
Rh-PEG NDs	Polyethylene glycol-coated ultrasmall rhodium nanodots metal nanocatalyst	Catalase	Clear reactive oxygen and nitrogen species; enhance photothermal performance	CT-26 cells and mouse models	[50]
BSA-Cu SAN	Proteins support copper single-atom nanozymes	Peroxidase	Eliminate the pathogen F. nucleatum within tumors to disrupt the pathogenic symbiosis in the tumor microenvironment	HCT116 cells and mouse models	[56]
LDH/MgO2 (BM)	Acid-hydrolyzed LDH-/MgO2-based pcCAT/pcLOX nanozymes	Catalase and lactate oxidase	Induce self-oxygenation and enhanced lactic acid consumption, as well as local immune activation and anti-angiogenesis through tumor microenvironment regulation	CT-26 cells and mouse models	[57]
Nano-Folox/Nano-FdUMP	Nanoprecipitation technology based on FOLFOX	Peroxidase	Mediates the formation of ROS and promotes immunogenic cell death-related anti-tumor immunity	CT26 and Hepa1-6 cells and mouse models	[58]
Pt-NP	ROS response to nano-prodrug (CPT-TK-Pa/Pt NP)	Peroxidase	Utilizes platinum nanozymes to catalyze the production of oxygen from hydrogen peroxide within tumors to alleviate hypoxia and enhance the efficacy of photodynamic therapy	CT-26 cells and mouse models	[65]
Ru@CeO2-RBT/ResDPEG	On-demand released dual-drug delivery system (Ru@CeO2-RBT/ResDPEG)	Peroxidase	Provide oxygen supply, deliver anti-cancer drugs, and enhance photothermal therapy	CT-26 cells and mouse models	[66]
AgNP; CatCry	Protein crystal base nanoparticles (CatCry-AgNP-DOX)	Catalase	Provide oxygen supply and facilitate the delivery of anti-cancer drugs	HCT116 cells and mouse models	[67]
BN-GDY	Non-metallic ferroptosis and apoptosis inducers based on boron and nitrogen co-doped graphdiyne (BN-GDY)	Peroxidase	Provide oxygen supply and induce ferroptosis and apoptosis	CT26 and HCT-116 cells and mouse models	[70]
N/C	Amorphous honeycomb nitrogen-doped carbon (N/C) nanozyme	NADH oxidase and catalase	Provide oxygen supply, facilitate the delivery of anti-cancer drugs, and induce cell apoptosis	HCT-116 cells and mouse models	[71]

F. nucleatum: Fusobacterium nucleatum; pcCAT: Partially cross-linked catalase; pcLOX: Partially cross-lactate oxidase.