Table 4.

Types of enzymes aberrantly expressed in tumor tissues and their specific cleavage substrates, corresponding vector functions.

Types of enzyme	High expression site	Specific cleavage substrate	Carrier design and function
Matrix metalloproteinases (MMP-2 and MMP-9 also known as gelatinase class)	Tumor extracellular microenvironment	GPLGIAGQ XGPLGV.PVGLIG	1)Target exposure of target molecules or membrane penetrating peptides 2)Tumor extracellular enzyme responsive drug release 3)Degradation of large particle size carriers to small particle size carriers for deep tumor penetration 4)Targeted removal of PEG shell to enhance uptake of nanocarriers by tumor cells
Prostate-specific antigen (PSA)	The extracellular microenvironment of prostate cancer	MuHSSKLQL.AcOmASKLQSL AcHypSSChgQSSP	1)Rapid release of precursor drug targets 2)Diagnosis of prostate cancer
Tissue proteinase B (CaB)	Tumor cell endosomes	GFLG	1)Rapid intracellular drug release in tumor cells 2)Enzyme-activated nanoprobes for diagnostic therapy
Phospholipase A2 (PLA2)	Tumor extracellular microenvironment or site of inflammation	DPPC, DSPE, DSPC, POPC, PLA, PCL, etc.	1)Enzyme-responsive drug release 2)Phospholipase sensor 3)Targeted drug delivery
α-Amylase	The extracellular microenvironment of the tumor or necrotic tumor area	Catalyzes the formation of small glucose molecules from polysaccharides. For example β-cyclodextrin, glycolic acid, etc.	the enzymatic action of drug release
Lysyl oxidase (LOX)	Highly expressed in the tumor extracellular matrix (ECM)	Antibody	Targeting LOX in the extracellular matrix of tumors, thereby altering the structure of ECM and inhibiting tumor growth and invasion
β-Glucuronidase	Necrotizing tumor area	Glucuronide	The enzymatic action of drug release
Fibroblast activation protein (FAP)	Cell-associated fibroblasts (CAF) surface	Hydrolysis of the N-terminal closed pro-X bond	Targeting CAF, killing the microenvironment on which tumor cells live, and thus killing tumor cells