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. 2026 Mar 9;17(4):1794–1810. doi: 10.1039/d6md00049e

Table 2. Summary of enzyme-responsive peptide linkers in PDC constructions.

Type of enzyme Representative peptides Cleavage site Key features
Cathepsin B Val-Cit Tumor endosomes • Clinically validated
Val-Ala • Heterogeneous payload release
• Strong hydrophobicity leads to easy aggregation
GFLG Tumor endosomes • Enhanced enzyme accessibility
• Sustained intracellular release
• Increased molecular weight and synthetic complexity
 
MMPs GPLGIAG Tumor extracellular microenvironment • High specificity for MMP-2/9
PLGLAG • High off-target risk in non-tumor tissues
PVGLIG
 
PSA SSKYQSL Prostate tumor extracellular microenvironment • PSA enzyme selectivity
• Prone to being affected by PSA expression levels
• Restrict in prostate cancer treatment