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Enzymatic Cascade Reactions inside Polymeric Nanocontainers: A Means to Combat Oxidative Stress

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2011
Author Tanner P., Onaca O., Balasubramanian V., Meier W., Palivan C. G.,
Project Nanostructured Polymers
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Original article (peer-reviewed)

Journal Chemistry-a European Journal
Volume (Issue) 17(16)
Page(s) 4552 - 4560
Title of proceedings Chemistry-a European Journal
DOI 10.1002/chem.201002782

Open Access

Abstract

Oxidative stress, which is primarily due to an imbalance in reactive oxygen species, such as superoxide radicals, peroxynitrite, or hydrogen peroxide, represents a significant initiator in pathological conditions that range from arthritis to cancer. Herein we introduce the concept of enzymatic cascade reactions inside polymeric nanocontainers as an effective means to detect and combat superoxide radicals. By simultaneously encapsulating a set of enzymes that act in tandem inside the cavities of polymeric nanovesicles and by reconstituting channel proteins in their membranes, an efficient catalytic system was formed, as demonstrated by fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy. Superoxide dismutase and lactoperoxidase were selected as a model to highlight the combination of enzymes. These were shown to participate in sequential reactions in situ in the nanovesicle cavity, transforming superoxide radicals to molecular oxygen and water and, therefore, mimicking their natural behavior. A channel protein, outer membrane protein F, facilitated the diffusion of lactoperoxidase substrate/products and dramatically increased the penetration of superoxide radicals through the polymer membrane, as established by activity assays. The system remained active after uptake by THP-1 cells, thus behaving as an artificial organelle and exemplifying an effective approach to enzyme therapy.
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