title: New concepts to fight oxidative stress: nanosized three-dimensional supramolecular antioxidant assemblies.
abstract: BACKGROUND
  Misregulation of reactive oxygen species and reactive nitrogen species by the body's antioxidant system results in oxidative stress, which is known to be associated with aging, and involved in various pathologies including cancer, neurodegenerative and cardiovascular diseases. A large variety of low-molecular-weight (LMW) antioxidant compounds and antioxidant enzymes have been proposed to alleviate oxidative stress, but their therapeutic efficacy is limited by their solubility, stability or bioavailability. In this respect, nanoscience-based systems are expected to provide more efficient mitigation of oxidative stress.
  
  
  METHODS
  The main nanoscience-based three-dimensional (3D) supramolecular assemblies, decorated with, or entrapping antioxidant compounds, or which possess intrinsic antioxidant activity are discussed and illustrated with recent examples. Assemblies with different architectures and sizes in the nanometer range serve: i) to deliver LMW antioxidant compounds or enzymes; ii) as antioxidant systems due to their intrinsic activity; and recently iii) to provide a confined space where catalytic antioxidant reactions take place in situ (nanoreactors and artificial organelles). A few insights into the role of antioxidants in mitigating oxidative stress caused by therapeutic compounds or drug carriers are also discussed.
  
  
  CONCLUSIONS
  Several challenges must still be overcome in the development of 3D supramolecular assemblies to efficiently fight oxidative stress. First, an improvement of the assemblies' properties and stability in biological conditions has to be addressed. Second, new systems based on the combination of biomolecules or mimics in supramolecular assemblies should provide multifunctionality, stimuli-responsiveness and targeting properties for a more efficient therapeutic effect. Third, comparative studies are necessary to evaluate these systems in a standardized manner both in vitro and in vivo.
authors.affiliation: University of Basel, Department of Chemistry , Klingelbergstrasse 80, CH 4056 Basel , Switzerland.
authors.forename: Pascal U
authors.initials: PU
authors.lastname: Richard
authors.forename: Jason T
authors.initials: JT
authors.lastname: Duskey
authors.forename: Svetlana
authors.initials: S
authors.lastname: Stolarov
authors.forename: Mariana
authors.initials: M
authors.lastname: Spulber
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: Palivan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012995:Solubility
chemical_list: D000975:Antioxidants; D004337:Drug Carriers; D017382:Reactive Oxygen Species
keywords: antioxidant delivery; antioxidant enzymes; artificial organelles; nanocarriers; nanoparticles; nanoreactors; oxidative stress; polymersomes; solid lipid nanoparticles