Abstract
T24
Introduction: Both acute and delayed cutaneous responses occur following injury from ionizing radiation. Currently there are no FDA approved preventive measures that would protect the skin from the effects of ionizing radiation other than the use of time, distance and shielding principles. Cerium oxide nanoparticles (nanoceria) have unique redox properties that can act as free-radical scavengers. Our preliminary results in breast cancer epithelial monolayer cells show that nanoceria conferred radioprotection at all tested nanoceria concentrations and at all tested radiation doses up to 10 Gy. This radioprotection increased in proportion to the nanoparticle concentrations with a corresponding decrease in reactive oxygen species at all tested radiation doses. To this end, we tested the safety of nanoceria for in vivo dermal applications in an animal model. Purpose: To demonstrate that unmodified nanoceria can be safely used in BALB/c mice for topical dermal applications towards radiobiological uses.
Methods: The dorsal skin of 6 mice was depilated in a 1cm x 1cm area using a shaving razor and cerium oxide nanoparticles at a concentration exceeding 200 microgram/cm2 was not applied (control, n=3) or applied (treated, n=3) using cotton tipped applicator two times a week for two weeks and visual observations were made for four weeks. By the end of 4 weeks, 0.2 mCi (7.4 MBq) of F18 FDG was administered intraocularly to both control and treated mice followed by 45 minutes of wait time and whole-body PET/CT imaging. Mice were sacrificed and dorsal skin was harvested, fixed in 3% glutaraldehyde and 1% paraformaldehyde in 0.1M cacodylate buffer, followed by post-fixation, dehydration, infiltration, embedding, thin sectioning, and transmission electron microscopy imaging.
Results: Our studies showed that: 1) Application of nanoceria to the dorsal skin of mice demonstrated no toxic effects to the skin or caused any pain or visible distress to the mice until 4 weeks of observation post treatment (Fig. 1). 2) PET/CT imaging of treated mice showed no evidence of variation in F-18 FDG uptake to the dorsal skin compared to the untreated control mice (fig. 2). 3) Transmission electron microscopy showed successful uptake of nanoceria into the epidermal skin layers (fig. 3).
Conclusions: Cerium oxide nanoparticles, when taken up in the mice epidermal skin layers, does not show any evidence of inflammatory responses and appears to be safe for use in dermal applications towards further radiobiological testing.
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