Ceria loaded nanoreactors: a nontoxic superantioxidant system with high stability and efficacy

Medical applications of the superantioxidant ceria nanoparticles (CeNP) are limited due to their high toxicity and low stability. CeNP toxicity is related to their aggregation in solution, and the possible generation of reactive oxygen species (ROS) by a Fenton-like reaction. For the efficient medical application of CeNP, it is necessary to find new solutions, which simultaneously reduce their inherent toxicity while preserving their unique catalytic regenerative qualities. Here we introduce a straightforward strategy based on CeNP encapsulation in polymer vesicles which reduces their toxicity, but preserves their superantioxidant character. We have engineered antioxidant nanoreactors, which serve the dual purpose of: (i) separation of CeNP, which inhibits aggregate formation, and (ii) protection of CeNP from hydrogen peroxide, thus eliminating the Fenton-like reaction which induces cytotoxicity. Nanoreactors containing CeNP possess a higher scavenging activity than free CeNP for both hydroxyl and superoxide radicals, as indicated by spin trapping EPR. Due to the regenerative redox chemistry of ceria, the nanoreactors are active for long periods of time, without requiring additional reducing agents. Upon uptake by cells, the nanoreactors show almost no toxicity compared with the free CeNP after a long term exposure, thus proving their high efficacy as ROS scavengers. Our strategy of engineering CeNP-containing nanoreactors represents a versatile, simple and economical solution to reduce CeNP toxicity, while preserving their functionality; thus nanoreactors are the ideal candidates for fighting oxidative stress in a large variety of medical situations.