title: Enzymatic cascade reactions inside polymeric nanocontainers: a means to combat oxidative stress.
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.
authors.affiliation: Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Tanner
authors.forename: Ozana
authors.initials: O
authors.lastname: Onaca
authors.forename: Vimalkumar
authors.initials: V
authors.lastname: Balasubramanian
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meier
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: Palivan
mesh_terms: D057487:Enzyme Therapy; D006801:Humans; D007784:Lactoperoxidase / Q000378:metabolism* / Q000648:ultrastructure; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000648:ultrastructure; D013481:Superoxides / Q000737:chemistry
chemical_list: D017382:Reactive Oxygen Species; D013481:Superoxides; D007784:Lactoperoxidase; D013482:Superoxide Dismutase