Enzyme-instructed self-assembly (EISA) assists the self-assembly and hydrogelation of hydrophobic peptides

Abstract

Enzyme-instructed self-assembly (EISA) has several advantages in the preparation of supramolecular self-assembly materials for biomedical applications. In this study, we demonstrated that the enzyme-instructed self-assembly (EISA) strategy could assist the...

Self-Assembled Peptide Nanostructures for ECM Biomimicry

“…The enzyme-instructed self-assembly (EISA) strategy was also applied to YIGSRcontaining peptides, to form a self-assembled hydrogel directly on HeLa cells overexpressing alkaline phosphatase (ALP), so that a phosphorylated gelator precursor (that was too hydrophilic to self-assemble) could be dephosphorylated in situ and gel [84]. Importantly, direct use of the non-phosphorylated Nap-GFFYIGSR was not effective due to its poor solubility in water, thus confirming the effectiveness of the EISA approach.…”

“…Another approach consisted of the use of Nap-GffyGYSV peptide, containing the Nap gelation moiety and D-amino acids to increase the gelation ability and resistance of the gel in biological environments [87]. A smarter strategy using the similar peptides Nap-Gff(p)YSV [88] and Nap-GFF(p)YSV [84] with a phosphorylated tyrosine was developed to selectively form a hydrogel via dephosphorylation of tyrosine with EISA, directly on cancer cells overexpressing alkaline phosphatase.…”

Intracellular Enzyme-Instructed Self-Assembly of Peptides (IEISAP) for Biomedical Applications

“…It is possible to use peptide-based small molecules to intracellularly polymerize and self-organize into three-dimensional (3D) nanostructures, which can be utilized as drug-free agents for cancer therapy. Therefore, drug-free IEISAP materials can be used directly as nanomedicines to modulate the fate of cancer cells [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ], leading to tumor apoptosis [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 102 ], necroptosis [ 93 , 94 , 95 , 97 , 102 ], autophagy [ 63 ], or cellular stress [ 98 , 99 ] ( Table 1 ). Most IEISAP materials cause apoptosis of cancer cells in diverse manners, such as blocking cellular mass exchange [ 83 ], disrupting mitochondria to release cytochrome c [ …”

“…The most frequently used enzyme that can induce the formation of IEISAP materials in cells or in vivo is ALP [ 83 , 84 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 94 , 95 , 96 , 97 , 100 , 103 ], and the less frequently used ones include esterase [ 99 ], carboxylesterase (CES) [ 93 , 100 ], transglutaminase (TGase) [ 85 ], ATG4B [ 63 ], reductase [ 90 ], furin [ 101 ], and trypsin [ 102 ]. Since cancer cells have higher levels of these enzymes than normal cells, the corresponding IEISAP materials may have the capacity to selectively target and kill cancer cells without harming the normal ones.…”

“…Since cancer cells have higher levels of these enzymes than normal cells, the corresponding IEISAP materials may have the capacity to selectively target and kill cancer cells without harming the normal ones. In ALP-overexpressing cancer cells, the peptide-derived small-molecule building blocks are dephosphorylated by ALP and then self-assembled into nanostructures, including nanonets [ 83 ], nanofibrils [ 87 , 92 ], nanoparticles [ 91 , 95 ], and hydrogels [ 103 ], which can be used for cancer treatments. For instance, Kuang et al reported the naphthalene-capped tripeptide D-1 (D-Phe-D-Phe-D-Tyr) in which Tyr could be dephosphorylated by ALP to generate the hydrogelator D-2 in the pericellular space, once encountering cancer cells overexpressing ALP, such as HeLa, MES-SA, and MES-SA/Dx5 [ 83 ].…”