Naslov
Customizing Morphology, Size, and Response Kinetics of Matrix Metalloproteinase-Responsive Nanostructures by Systematic Peptide Design

Autori
Son, Jiye ; Kalafatovic, Daniela ; Kumar, Mohit ; Yoo, Barney ; Cornejo, Mike A. ; Contel, María ; Ulijn, Rein V.

Izvornik
ACS nano (1936-0851) 13 (2019), 2; 1555-1562

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
electrostatic enzyme interactions ; enzyme kinetics ; MMP-responsive ; morphology change ; self-assembling peptides ; supramolecular organization

Sažetak
Overexpression and activation of matrix metalloproteinase-9 (MMP-9) is associated with multiple diseases and can serve as a stimulus to activate nanomaterials for sensing and controlled release. In order to achieve autonomous therapeutics with improved space-time targeting capabilities, several features need to be considered beyond the introduction of an enzyme- cleavable linker into a nanostructure. We introduce guiding principles for a customizable platform using supramolecular peptide nanostructures with three modular components to achieve tunable kinetics and morphology changes upon MMP- 9 exposure. This approach enables (1) fine- tuning of kinetics through introduction of ordered/disordered structures, (2) a 12- fold variation in hydrolysis rates achieved by electrostatic (mis)matching of particle and enzyme charge, and (3) selection of enzymatic reaction products that are either cell-killing nanofibers or disintegrate. These guiding principles, which can be rationalized and involve exchange of just a few amino acids, enable systematic customization of enzyme- responsive peptide nanostructures for general use in performance optimization of enzyme-responsive materials.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA