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Supramolecular Design of Unsymmetric Reverse Bolaamphiphiles for Cell‐Sensitive Hydrogel Degradation and Drug Release
Author(s) -
Chakroun Rami W.,
Sneider Alexandra,
Anderson Caleb F.,
Wang Feihu,
Wu PeiHsun,
Wirtz Denis,
Cui Honggang
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201913087
Subject(s) - supramolecular chemistry , biophysics , micelle , substrate (aquarium) , peptide , chemistry , nanotechnology , drug delivery , cell , materials science , biochemistry , biology , crystallography , ecology , aqueous solution , crystal structure
Self‐assembly of peptide‐based building units into supramolecular nanostructures creates an important class of biomaterials with robust mechanical properties and improved resistance to premature degradation. Yet, upon aggregation, substrate–enzyme interactions are often compromised because of the limited access of macromolecular proteins to the peptide substrate, leading to either a reduction or loss of responsiveness to biomolecular cues. Reported here is the supramolecular design of unsymmetric reverse bolaamphiphiles (RBA) capable of exposing a matrix metalloproteinase (MMP) substrate on the surface of their filamentous assemblies. Upon addition of MMP‐2, these filaments rapidly break into fragments prior to reassembling into spherical micelles. Using 3D cell culture, it is shown that drug release is commensurate with cell density, revealing more effective cell killing when more cancer cells are present. This design platform could serve as a cell‐responsive therapeutic depot for local chemotherapy.