Abstract

Cerium oxide nanoparticles (nanoceria), well known for their pro- and antioxidant features, have been recently proposed for the treatment of several pathologies, including cancer and neurodegenerative diseases. However, interaction between nanoceria and biological molecules such as proteins and lipids, short blood circulation time, and the need of a targeted delivery to desired sites are some aspects that require strong attention for further progresses in the clinical application of these nanoparticles. The aim of this work is the encapsulation of nanoceria into a liposomal formulation in order to improve their therapeutic potentialities. After the preparation through a reverse-phase evaporation method, size, Z-potential, morphology, and loading efficiency of nanoceria-loaded liposomes were investigated. Finally, preliminary in vitro studies were performed to test cell uptake efficiency and preserved antioxidant activity. Nanoceria-loaded liposomes showed a good colloidal stability, an excellent biocompatibility, and strong antioxidant properties due to the unaltered activity of the entrapped nanoceria. With these results, the possibility of exploiting liposomes as carriers for cerium oxide nanoparticles is demonstrated here for the first time, thus opening exciting new opportunities for in vivo applications.

Highlights

  • In cerium oxide, Ce owns the peculiar ability to switch between two oxidation states, Ce3+ and Ce4+, through the loss of electrons and/or oxygen, giving origin to crystalline defects or vacancies on the surface of the material [1]

  • The discovery of the excellent catalytic activities of nanoceria and their ability to act as free radicals scavengers have opened new perspectives in the biomedical fields and, in all those scenarios where oxidative stress plays a crucial role in the pathogenesis of diseases [2]

  • We demonstrate for the first time that nanoceria can be encapsulated inside liposomes preserving their antioxidant activities

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Summary

Introduction

Ce owns the peculiar ability to switch between two oxidation states, Ce3+ and Ce4+, through the loss of electrons and/or oxygen, giving origin to crystalline defects or vacancies on the surface of the material [1]. The biological activities of cerium oxide nanoparticles were assessed in vitro on several cell culture models such as cardiac [4], neuronal [5], and stem cells [6]; in vivo, nanoceria showed strong antioxidant properties by decreasing both nitric oxide and peroxynitrite formation in a murine model of ischemic cardiomyopathy [7], and they slowed down the progression of retinal degeneration in mouse and rat models [8,9], promoted the regression of retinal vascular lesions in mice [10], and inhibited weight gain in rats [11] Another peculiar feature of cerium oxide nanoparticles is their ability to act as a pro-oxidant agent at acidic pH values [12]. Anticancer activity of nanoceria was studied in vitro for the treatment of breast, pancreas, ovarian, lung, and colon cancer cells [15,16,17]

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