Glycooligomer-Functionalized Catalytic Nanocompartments Co-Loaded with Enzymes Support Parallel Reactions and Promote Cell Internalization.
Maria KorpidouJonas BeckerShabnam TarvirdipourIonel Adrian DinuCaglar Remzi BecerCornelia G PalivanPublished in: Biomacromolecules (2024)
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 H 2 O 2 . 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 H 2 O 2 . 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.
Keyphrases
- cancer therapy
- single cell
- reactive oxygen species
- drug delivery
- cell therapy
- emergency department
- quantum dots
- stem cells
- nitric oxide
- cell death
- blood pressure
- dna damage
- mesenchymal stem cells
- adipose tissue
- hydrogen peroxide
- skeletal muscle
- gold nanoparticles
- high resolution
- weight loss
- wound healing
- reduced graphene oxide
- liquid chromatography