Table 1.

Chemical triggers described in this review.

Chemical trigger	Structure	Mechanism	Payload	Ref.
Acid cleavable triggers	Hydrazone trigger	Linkers cleavage by low pH of tumor acidic microenvironment or lysosomes	Calicheamicin	10
	Carbonate trigger		SN-38	27
	Silyl ether trigger		MMAE	28
GSH cleavable trigger	Disulfide trigger	Linkers cleavage by high level of GSH in cytoplasm	DM1, DM3, MMAE	30
			PBD	31
Fe(II) cleavable trigger	1,2,4-Trioxolane trigger	Linker cleavage by elevating levels of ferrous iron	MMAE	34
Cathepsin cleavable triggers	Dipeptide trigger	Linkers cleavage by cathepsin in lysosomes	MMAE, DM1	21
	Triglycyl (CX) trigger		DM1	22
	cBu-Cit trigger		MMAE, PBD	20
Glycosidase cleavable triggers	β-Glucuronide trigger	Linkers cleavage by β-glucuronidase in lysosomes	MMAE	35
	β-Galactoside trigger	Linkers cleavage by β-galactosidase in lysosomes	MMAE	36
Phosphatase cleavable triggers	Pyrophosphate trigger	Linkers cleavage by phosphatase and pyrophosphates in lysosomes	Budesonide	18
Sulfatase cleavable trigger	Arylsulfate trigger	Linkers cleavage by sulfatase in lysosomes	MMAE	37
Photo-responsive cleavable triggers	Heptamethine cyanine fluorophore trigger	Linkers cleavage by irradiation with NIR light (λ = 650–900 nm)	CA-4	46
	O-Nitrobenzyl trigger	Linkers cleavage by irradiation with UV light (λ = 365 nm)	MMAE	47
	PC4AP trigger	Linkers cleavage both by irradiation with near-infrared (NIR) light (λ = 365 nm) and intramolecular addition reaction with nearby amine	DOX	48
Bioorthogonal cleavable trigger	dsProc trigger	Linkers cleavage by the bioorthogonal cleavage pair: Cu(I)-BTTAA/dsProc	DOX	55
Non-cleavable linkers	MD linker	No linker cleavage, ADCs metabolizes amino acid appendage, a linker and molecule cytotoxicity upon entry lysosome	TRMRA	14
	PEG linkers with intermediates of alkyne, triazole and piperazine		PBD Dimer	58
	Mal-PAB linker		MMAE	59