TABLE 2

Brief summary of the stimuli-responsive peptides and their applications

StimuliPeptide SequenceTherapeutic StrategyResultReferences
EnzymesGPLG↓IAGQ (MMP-2)Linked protective PEG to CPP-modified liposome via MMP-2-responsive sequenceEnhanced target ability and internalization of nanocarriers in cancer cellsZhu et al., 2012
PVG↓LIG (MMP-2/9)Gao et al., 2013
GP↓AX (FAP-α)Ji et al., 2016b
AcidosisACEQNPIYWARYADWLFTTPLLLLDLALLVDADEGTGCombined pH LIP with a microRNA miR-155 via disulfide bondDelivery of miR-155 specifically to tumor site and efficient uptake by tumor cellsAndreev et al., 2007
H7Conjugated cell-penetrating peptide (R2)2 and H7 modify to polymeric micelleActivation of cell-penetrating peptide by response of H7 to the acidic tumor microenvironmentZhao et al., 2016
E4K4Mask to a cell-penetrating peptide via linking by an enzyme-responsive cleavable sequenceCell-penetrating peptide exposed via E4K4 charge transforming and linker cleavingHuang et al., 2013a
HyperthermiaVSSLESKVSSLESKVSKLESKKSKLESKVSKLESKVSSLESKLeucine zipper peptide-lipid hybrid nanovesicles loaded with Dox insideSuperior serum stability at physiologic temperature and increased drug accumulation in tumorAl-Ahmady et al., 2012
(VPGVG)40(VPGXG)60Temperature triggered activation of the cell penetrating ability of ELP-penta-arginine copolymerThermal triggered copolymer assembly increased the local density of arginine and the cell penetrating activity at higher temperatureMacewan and Chilkoti, 2012
X=A:G; 1:1
  • ELPs, Elastin-like polypeptides; X: any amino acid;↓: cleavable site.