期刊
ADVANCED MATERIALS
卷 34, 期 1, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202104962
关键词
cellular uptake; enzyme-responsive materials; matrix metalloproteinase; nanomedicine; peptides; self-assembly; zwitterionic nanoparticles
类别
资金
- National Science Foundation
- NSF DMR [1461499]
- NSF CREST-IDEALS [1547830]
- NSF [CHE 1808143]
- United States-Israel Binational Science Foundation (BSF), Jerusalem, Israel [2017510]
- CUNY-Strathclyde program
- National Institutes of Health (NIH) [2SC1GM127278-07A1]
- Divn Of Social and Economic Sciences
- Direct For Social, Behav & Economic Scie [2017510] Funding Source: National Science Foundation
The study demonstrates the use of zwitterionic tetrapeptide modalities to direct nanoparticle assembly under physiological conditions, allowing for the reduction of cell growth in cancer cells through enzyme-responsive self-assembly. Customizing the peptide sequence can program the enzyme responsiveness and cellular uptake pathway.
Supramolecular self-assembly in biological systems holds promise to convert and amplify disease-specific signals to physical or mechanical signals that can direct cell fate. However, it remains challenging to design physiologically stable self-assembling systems that demonstrate tunable and predictable behavior. Here, the use of zwitterionic tetrapeptide modalities to direct nanoparticle assembly under physiological conditions is reported. The self-assembly of gold nanoparticles can be activated by enzymatic unveiling of surface-bound zwitterionic tetrapeptides through matrix metalloprotease-9 (MMP-9), which is overexpressed by cancer cells. This robust nanoparticle assembly is achieved by multivalent, self-complementary interactions of the zwitterionic tetrapeptides. In cancer cells that overexpress MMP-9, the nanoparticle assembly process occurs near the cell membrane and causes size-induced selection of cellular uptake mechanism, resulting in diminished cell growth. The enzyme responsiveness, and therefore, indirectly, the uptake route of the system can be programmed by customizing the peptide sequence: a simple inversion of the two amino acids at the cleavage site completely inactivates the enzyme responsiveness, self-assembly, and consequently changes the endocytic pathway. This robust self-complementary, zwitterionic peptide design demonstrates the use of enzyme-activated electrostatic side-chain patterns as powerful and customizable peptide modalities to program nanoparticle self-assembly and alter cellular response in biological context.
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