Table 2.
Key hydrolases of enzyme-sensitive drug delivery systems.
| Class | Enzyme | Substrate | Position | Functions | |
|---|---|---|---|---|---|
| Proteases | CAPs (MMP-1/MMP-2/MMP-9) |
GPLGVRGK, GPLGIAGQ, PVGLIP, PLGLAGr9 peptides, gelatin | Extracellular | Size-shrinking [116, 192] PEG deshielding [61,193] Drug release [194, 195] Morphology switch [196, 197] |
|
| Proteases | Lysosomal enzyme (Cathepsin B) | GFLG peptide, Biotin-avidin system |
Intracellular (mainly lysosome) |
Drug release [198] Cap system [150, 199] |
|
| Proteases | FAP-α | DRGETGPAC | Extracellular (mainly CAFs) | Fluorescence release [200] | |
| Peptidase | Amino peptidase |
Unacylated amino acids | Extracellular | CPP activation [201] | |
| Peptidase | Dipeptidyl peptidase IV | Xaa-Pro dipeptides | Extracellular | CPP activation [201] | |
| Lipases | PLA2 | Phospholipids with a non-hydrolyzable ether bond in the 1-position, di(ethylene glycol) diacrylate hyaluronic acid | Extracellular | Drug release [202, 203] Cellular uptake [204] Size shrinking [205] |
|