Customizing Morphology, Size, and Response Kinetics of Matrix Metalloproteinase-Responsive Nanostructures by Systematic Peptide Design.
ACS Nano
; 13(2): 1555-1562, 2019 02 26.
Article
en En
| MEDLINE
| ID: mdl-30689363
ABSTRACT
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Metaloproteinasa 9 de la Matriz
/
Metaloproteinasas de la Matriz
/
Nanoestructuras
Idioma:
En
Revista:
ACS Nano
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos