Green synthesized cerium oxide nanoparticle: A prospective drug against oxidative harm

https://doi.org/10.1016/j.colsurfb.2016.07.045Get rights and content

Highlights

  • Green synthesis of cerium oxide nanoparticle using aloe vera extract.

  • Absorbed organic layer on the surface of the nanoparticles forming biogenic corona.

  • Effective antioxidant against radical-induced damages in mouse neuroblastoma cells.

  • Nanoparticle shows uninterrupted antioxidant property due to its oxidation states.

  • No toxic role of the nanoparticle was found in cells.

Abstract

Cerium oxide nanoparticle (CeONP) of size 2–3 nm was synthesized by a new, simple and green method at ambient temperature, using cerium nitrate as prime precursor and Aloe vera leaf extract as stabilizing agent. Of the two oxidation states (+3) and (+4) of cerium, it was dominantly present in (+3) state in CeONP and cyclic conversion of Ce(III)O  Ce(IV)O  Ce(III)O by reaction with H2O2 implied uninterrupted antioxidant property of CeONP. Moreover, the higher oxygen defect in the crystal lattice produced particles with higher antioxidant activity. CeONP was found to neutralize the deleterious effects of H2O2 viz., cell death, generation of intracellular reactive oxygen species and loss of connectivity in mouse neural cells. Therefore, CeONP might have potential use in future as an anti-oxidant drug.

Introduction

Oxidative stress has been implicated as a cause of different diseases like arthritis, cardiac disorder, diabetes, Alzheimer’s and Parkinson’s diseases, macular and retinal degeneration etc. [1], [2]. Cellular oxidative damage is mediated by ‘reactive oxygen species’ (ROS), which include free radicals such as superoxide anion (O2radical dot), hydroxyl radical (radical dotOH), singlet oxygen (1O2) and non-free radical species like hydrogen peroxide (H2O2). Usually, antioxidants protect cells from oxidative stress, by neutralizing ROS. Most of the antioxidants are exhausted to neutralize ROS; however, cerium oxide (CeO) has an exclusive uninterrupted antioxidant activity, because cerium can cycle between the cerous (Ce3+) and ceric (Ce4+) oxidation states. CeO(III) is fast oxidized to CeO(IV) by ROS and by that CeO(III) successfully neutralizes ROS. Again CeO(IV) is slowly reduced by ROS to slip back to CeO(III), leaving oxygen vacancies in the CeO crystal lattice that becomes further reactive towards ROS [3], [4]. Thus, cycling of CeO between +3 and +4 states can uninterruptedly break down ROS.

Over the past few years there has been increasing research to explore the therapeutic capacity of nanoscale cerium oxide [5], [6], [7], [8], [9]. Thermal history of synthesis of CeO2 nanoparticles is suggested to be a factor that strongly influences the biological impact of nano-ceria. Synthesis methods, involving high temperature exposure, produce CeONP of pro-oxidative inflammatory response; on the other hand, methods requiring low heat or room temperature form particles of anti-oxidative response [10], [11]. Moreover, various chemical processes of synthesis produce nanoparticles with undesirable functionality. We, therefore, ventured to synthesize biocompatible CeONP of potential antioxidant activity.

In this communication we report about a simple, green method of preparation of CeONP at room temperature, using cerium nitrate [Ce(NO3)3] as the prime precursor and Aloe vera leaf extract as the stabilizing agent. Important physico-chemical characteristics of the synthesized CeONP have also been reported here. The organic layer of Aloe vera on the CeONP surface made it prone to interact with biological cell surface and thereby facilitated its internalization into the cell. Our CeONP has high pharmacological potential to neutralize the H2O2-induced oxidative stress in mouse neuroblastoma cells (N2A).

Section snippets

Preparation of aloe vera leaf extract

Fresh leaf pulp (30 g) of Aloe vera was boiled in 100 ml distilled water for 10 min. The aqueous extract was then filtered through Whatman filter paper-40 (GE Healthcare, UK). The filtrate was centrifuged at 15000 RPM for 15 min to remove any un-dissolved substance; the supernatant was collected and stored at −20 °C.

Synthesis of CeONP

For preparation of 10 ml CeONP suspension, 1 ml cerium nitrate (10 mM), 1 ml aqueous Aloe vera leaf extract and 7 ml Milli-Q water were first mixed at room temperature (28 °C); 1 ml of sodium

Preparation of CeONP

In the process of synthesis of the NPs, addition of cerium nitrate to Aloe vera extract made the pH of the mixture 6.0. By the subsequent addition of NaOH, pH of the mixed solution initially increased to 8.5, but after 48 h of consumption of OH ions, it finally became 7.5 with formation of cerium oxide. Such slow oxidation might be due to the fact that NaOH was a poor oxidizing agent. In order to check whether the Aloe-Vera extract acted as the stabilizing agent, we tried to synthesize CeONP,

Conclusion

This communication reports about a new, green method of preparation of biocompatible cerium oxide nanoparticles from cerium nitrate at room temperature, using Aloe vera extract as oxidizing as well as stabilizing agent. Major amount of cerium present in CeONP was in the Ce(III) oxidation state. Incubation of CeONP with H2O2 oxidized Ce(III) to Ce(IV) quickly in the time scale of minutes, whereas prolonged incubation converted Ce(IV) to Ce(III) slowly in time scale of days, signifying the

Acknowledgements

We are indebted to the a) University of Kalyani, for supporting the first author with fellowship and some contingency, b) Department of Science and Technology, Govt. of India for the ‘FIST’ and ‘PURSE’ Programs, and University Grants Commission, Govt. of India for the SAP Program of the department, for providing different instrumental and infrastructural support and c) Mr. Goutam Sarkar, scientific assistant of Saha Institute of Nuclear Physics for the help in taking the XPS data.

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