Glycooligomer-Functionalized Catalytic Nanocompartments Co-Loaded with Enzymes Support Parallel Reactions and Promote Cell Internalization.
Biomacromolecules
; 25(7): 4492-4509, 2024 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-38910355
ABSTRACT
A major shortcoming associated with the application of enzymes in drug synergism originates from the lack of site-specific, multifunctional nanomedicine. This study introduces catalytic nanocompartments (CNCs) made of a mixture of PDMS-b-PMOXA diblock copolymers, decorated with glycooligomer tethers comprising eight mannose-containing repeating units and coencapsulating two enzymes, providing multifunctionality by their in situ parallel reactions. Beta-glucuronidase (GUS) serves for local reactivation of the drug hymecromone, while glucose oxidase (GOx) induces cell starvation through glucose depletion and generation of the cytotoxic H2O2. The insertion of the pore-forming peptide, melittin, facilitates diffusion of substrates and products through the membranes. Increased cell-specific internalization of the CNCs results in a substantial decrease in HepG2 cell viability after 24 h, attributed to simultaneous production of hymecromone and H2O2. Such parallel enzymatic reactions taking place in nanocompartments pave the way to achieve efficient combinatorial cancer therapy by enabling localized drug production along with reactive oxygen species (ROS) elevation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glucose Oxidase
/
Peróxido de Hidrogênio
Limite:
Humans
Idioma:
En
Revista:
Biomacromolecules
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça