期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 59, 期 11, 页码 4434-4442出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201913087
关键词
anticancer; drug delivery; hydrogels; nanostructures; self-assembly
资金
- National Science Foundation [DMR 1255281, 1746891]
- NSF Graduate Research Fellowships Program [DGE 1746891]
- Direct For Education and Human Resources
- Division Of Graduate Education [1746891] Funding Source: National Science Foundation
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.
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