(426g) Protein Aggregation on Metal-Oxide Nanozymes Governs Activity and Cellular Uptake | AIChE

(426g) Protein Aggregation on Metal-Oxide Nanozymes Governs Activity and Cellular Uptake

Authors 

Dennebouy, L., Nanoparticle Systems Engineering Laboratory
Gogos, A., Particles-Biology Interactions
Pais, M. A., Department of Plastic and Hand Surgery
Neuer, A. L., Empa
Zimmermann, M., Nanoparticle Systems Engineering Laboratory
Lese, I., University Hospital Bern
Herrmann, I., University Hospital Zurich
Catalytically active inorganic nanomaterials offer promising prospects for biomedicine. Inorganic enzyme mimicking nanoparticles, termed nanozymes, have enabled fascinating applications, including attenuation of ischemia/reperfusion injury, and improved wound healing through radical scavenging and cell protection. Similarly, metal oxides can also be employed to generate radicals and induce cell death, for example in photodynamic or radiotherapy scenarios. When applying these nano-enzymes into a biological system, proteins rapidly physisorb on the surface of the metal oxide nanozymes, thus altering their physiochemical properties. We quantified and characterized the fraction of adsorbed proteins by proteomic analysis and linked the observed proteins to the nanoparticle fate in vivo. Opsonization of nanozymes led to an enhanced uptake by macrophages following topical application of the metal oxide nanozyme suspensions, and particle largely remained at the site of application (>99%). The enzyme mimicking activity was affected by the presence of proteins to a variable extent, suggesting that shielding of the nanoparticle surface by proteins needs to be taken into account in the development of catalytically active nanomaterials. Finally, we present potential strategies for the prevention and recovery of the catalytical activity based on metal oxide nanoparticle surface engineering. In summary, we investigated the influence of physiosorbed proteins on radical scavenging and radical generation based on a selection of catalytically active metal oxide nanoparticles, combining state-of-the-art proteomics and nanoanalytics, providing design criteria for high performance nanocatalysts exhibiting activity in complex biological environments.