Table 2.
pH-, reduction-, and enzyme-responsive micelles for protein/peptide delivery through the covalent approach (see Figure 3).
| Copolymer | Protein/Peptide | Stimulus | Linkage | Results | Ref. |
|---|---|---|---|---|---|
| POEGMA-PDMA-PDEA | Lysozyme | pH | Imine | Bioconjugation assessment | [79] |
| PLA-PEG-PLA | Lisinopril | pH | Ester | Improved drug loading stability at pH 7.4 (and release at pH 4) | [80] |
| Polyglutamate-PEG based | Ribonuclease A a | pH | phenylboronic acid–catechol | Enhanced intracellular release, enhanced anticancer efficacy | [81] |
| PDPA/PDMA based | Ovalbumin Lytic peptide |
Reduction | Disulfide | Improved immune responses (vaccines) | [82,83,84,85,86,87] |
| Proapoptotic peptide (BIM) | Reduction | Disulfide | Suppression of tumor growth | [88] | |
| Poly(lactide-co-glycolide)-PEG | Cytochrome C | Reduction | Disulfide | Endosomal escape, potential for antitumor therapy (brain model) | [89] |
| PDMA/PDPA based | Proapoptotic peptide (BIM) | Enzyme (cathepsin B) | FKFL cleavable sequence |
Improved intracellular delivery, Successful cancer cell apoptosis | [90] |
| PAsp(Bz)-PEG | PD-L1 antibody b | Enzyme (MMP2) | GGPLGVRGG cleavable sequence | Improved intracellular delivery, improved antitumor effect | [91] |
| Polynorbornene based | - | Enzyme (MMP2/9) | GPLGLAG cleavable sequence | Specific accumulation in infarcted heart | [92,93] |
a Co-delivery with hydrophobic doxorubicin drug. b Co-delivery with hydrophobic Zn phthalocyanine photosensitizer.