Protein Aggregation on Metal Oxides Governs Catalytic Activity and Cellular Uptake

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 20; no. 34; pp. e2311115 - n/a
• Main Authors: Nißler, Robert, Dennebouy, Lena, Gogos, Alexander, Gerken, Lukas R.H., Dommke, Maximilian, Zimmermann, Monika, Pais, Michael A., Neuer, Anna L., Matter, Martin T., Kissling, Vera M., Brot, Simone, Lese, Ioana, Herrmann, Inge K.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.08.2024
• Subjects: Animals; Biological activity; Biomedical materials; Catalysis; Catalytic activity; Cell death; Design optimization; Design parameters; Humans; In vitro methods and tests; In vivo methods and tests; Macrophages; Macrophages - metabolism; Metal oxides; Metals - chemistry; Mice; nanocatalyst; Nanomaterials; nanozyme; Oxides - chemistry; Protein Aggregates; protein corona; Protein Corona - chemistry; Protein Corona - metabolism; Proteins; Radiation therapy; RAW 264.7 Cells; Wound healing; nanocatalyst; wound healing; nanozyme; metal oxides; protein corona
• ISSN: 1613-6810; 1613-6829; 1613-6829
• DOI: 10.1002/smll.202311115

Engineering of catalytically active inorganic nanomaterials holds promising prospects for biomedicine. Catalytically active metal oxides show applications in enhancing wound healing but have also been employed to induce cell death in photodynamic or radiation therapy. Upon introduction into a biological system, nanomaterials are exposed to complex fluids, causing interaction and adsorption of ions and proteins. While protein corona formation on nanomaterials is acknowledged, its modulation of nanomaterial catalytic efficacy is less understood. In this study, proteomic analyses and nano‐analytic methodologies quantify and characterize adsorbed proteins, correlating this protein layer with metal oxide catalytic activity in vitro and in vivo. The protein corona comprises up to 280 different proteins, constituting up to 38% by weight. Enhanced complement factors and other opsonins on nanocatalyst surfaces lead to their uptake into macrophages when applied topically, localizing >99% of the nanomaterials in tissue‐resident macrophages. Initially, the formation of the protein corona significantly reduces the nanocatalysts' activity, but this activity can be partially recovered in endosomal conditions due to the proteolytic degradation of the corona. Overall, the research reveals the complex relationship between physisorbed proteins and the catalytic characteristics of specific metal oxide nanoparticles, providing design parameters for optimizing nanocatalysts in complex biological environments. Engineering inorganic nanomaterials for biomedicine offers potential from wound healing to cancer therapies. However, upon contact with biological fluids, proteins adsorb, altering the particle's properties through protein corona formation. This study correlates adsorbed proteins with metal oxide catalytic activity and cellular uptake, paving the way for optimizing nanocatalysts for biological settings.