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

Abstract

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.

A novel synthetic approach of cerium oxide nanoparticles with improved biomedical activity

“…C4 scavenged HO ● much less than the other CNP samples, in agreement with their tendency to agglomerate; the reduced CNP active area impaired their redox activity. Interestingly, C2 spectra showed some traces of DMPO-OOH abduct characterized by a A N 14.12 G, and A H of 11.3 G hyperfine coupling constants 27, 67 , superimposed to the DMPO-OH residual spectra (Fig. 5a).…”

“…Since the lifetime of HO ● at room temperature is very low (100 μs), the HO ● formation and decay in the presence of CNPs was studied using DMPO spin trap. The ESR spin trap technique takes advantage of spin trap molecule ability to react with free radicals, forming a more stable spin adduct with paramagnetic parameters that depend on the nature of the trapped radical 67 . In this work, the CNP redox activity was estimated by quantifying the formation of DMPO adducts in the absence (Fig.…”

“…In the absence of CNPs, the typical DMPO-OH spectrum was detected, consisting of four lines with peak intensity ratios of 1:2:2:1 and hyperfine coupling constants A N and A H for 14N and 1H equal to 14.9 G (Fig. 5a) 67, 68 . All the CNPs significantly reduced the DMPO-OH signal, showing a strong HO ● scavenging activity.…”

Cerium oxide nanoparticles in neuroprotection and considerations for efficacy and safety

“…In the materials industry, CeONPs are known for their oxygen storage capacity-their ability to take up and release oxygen in a redox reaction, through the creation and annihilation of oxygen vacancies. 45,46 In the biomedical realm, we appear to have neglected to think about this aspect of CeONPs when considering their action in vivo. When a valence change from +4 to +3 occurs, oxygen is usually released to the environment, depending on the oxygen partial pressure.…”

Engineering the defect state and reducibility of ceria based nanoparticles for improved anti-oxidation performance

“…37 Furthermore, there are some contradictory results in the previous works about the active sites of ceria NPs and the anti-oxidation process. [34][35][36][37][38] Here, we monitored the anti-oxidation process of CeO 2 NPs with H 2 O 2 and engineered the anti-oxidation performance by Gd 3+ doping. There are many unresolved questions about the anti-oxidation mechanism of ceria NPs, such as how absorption spectrum, medium species, coordination environment and surface state evolve during the anti-oxidation process.…”