Self-Complementary Zwitterionic Peptides Direct Nanoparticle Assembly and Enable Enzymatic Selection of Endocytic...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Molecular Biology

Background:

• Supramolecular self-assembly can translate disease signals into physical cues for cell fate modulation.
• Designing stable, tunable, and predictable self-assembling systems for physiological conditions remains a challenge.

Purpose of the Study:

• To report the use of zwitterionic tetrapeptide modalities for directing nanoparticle assembly under physiological conditions.
• To investigate enzyme-responsive nanoparticle self-assembly for cancer cell targeting.

Main Methods:

• Utilized gold nanoparticles functionalized with zwitterionic tetrapeptides.
• Activated nanoparticle self-assembly via enzymatic cleavage of peptides by matrix metalloprotease-9 (MMP-9).
• Investigated size-induced cellular uptake mechanisms and effects on cancer cell growth.

Main Results:

• Achieved robust nanoparticle assembly through multivalent, self-complementary zwitterionic tetrapeptide interactions.
• Demonstrated that MMP-9 overexpressed in cancer cells triggers nanoparticle assembly near the cell membrane.
• Observed diminished cancer cell growth due to size-induced selection of cellular uptake.
• Showed that peptide sequence customization can program enzyme responsiveness and alter cellular uptake pathways.

Conclusions:

• Zwitterionic tetrapeptides provide a robust platform for programming nanoparticle self-assembly in a biological context.
• Enzyme-activated electrostatic side-chain patterns offer customizable modalities to alter cellular responses.
• This approach holds potential for developing targeted cancer therapies by modulating cellular uptake mechanisms.