CeO2 Nanoparticles-assisted stem-based cell therapy: an innovative nanopharmaceutical approach to treat retinal degenerative diseases-CELLUX (CELLUX)

The main aim of the CELLUX project was to develop a novel pharmaceutical based on CeO2 nanoparticles (NPs) in the form of eye drops to treat Age-Related Macular Degeneration (AMD).

This treatment, in combination with stem cell-based therapeutic strategies, aims to halt degeneration and restore vision. The progression of AMD is associated with an increase in oxidative stress and inflammatory responses in the eye, leading to retinal cell death. This chronic disease is a major cause of blindness in elderly people and affects millions worldwide. CeO2 NPs have antioxidant properties due to their unique electronic structure; when reduced to the nanoscale, oxygen defects appear on their surface, serving as sites for free radical scavenging.

Within the project, CeO2-NPs were developed to regulate cellular redox potential and protect tissue from oxidative stress. Nanoceria eye drops were formulated, and treatment with these drops reduced the loss of retinal cells and visual dysfunction, as well as decreased inflammation. In combination with retinal pigment epithelial (RPE) cell transplants, increased RPE cell survival was demonstrated in rats, along with improved retinal light responses.

We demonstrated that such antioxidant therapy is a promising approach for enhancing the efficacy of RPE cell therapy in retinal degenerative diseases. Safety assessments of the nanoceria were performed in various models, and no hazardous potential was detected. Additionally, no irritation to human corneal epithelium was observed, confirming that the eye drop formulation is safe for ocular application.

NILU studied the safety of CeO2 NPs using in vitro models, measuring both the induction of cell death and DNA damage. Furthermore, the mechanisms of CeO2 NPs interaction with cells were studied using confocal microscopy, and the antioxidant protective effects of CeO2-NPs were compared with those of known antioxidants.

The project was financed through the ERA-NET EuroNanoMed3 program and was coordinated by the University Hospital (VHIR) in Barcelona. The consortium consisted of six partners from five countries: Spain, Norway, Italy, the Czech Republic, and France.
The results of the project are promising and will be published in scientific journals, even after the project is completed. Furthermore, the results will be used in new applications for research funding to achieve a higher Technology Readiness Level (TRL), with the goal of developing and producing eye drops for the treatment of patients with age-related macular degeneration.