Profiling the Anti-Photoaging Impact of Titanium Dioxide and Zinc Oxide Nanoparticles: A Focus on Signaling Pathways

Inorganic nanoparticles are known to protect skin from ultraviolet rays (UVR) and delay photoaging. However, the photoprotective effects of these nanoparticles have not been broadly analyzed at a genetic level. The study objectives are as follows: (1) to investigate how UV-only and complete solar light can affect signaling pathways and genes related to photoaging in human dermal fibroblasts; (2) to investigate how TiO₂ and ZnO nanoparticles provide photoprotection at a genetic level. RNAseq identified pathways and genes that were significantly affected by both irradiation conditions. Extracellular matrix (ECM) remodeling, inflammation, and cell cycle-related genes were subsequently validated by qPCR. The photoprotective properties of < 100 nm TiO₂ and ZnO dispersions at a 25% active level were analyzed through quantitative differences in the irradiation-induced expression of these genes. There were < 15 signaling pathways affected by UV and complete solar light (p-value (-log10) > 1). Significant differences in gene expression following irradiation were found in MMP1, MMP3, PTGS1, PTGES, MDM2, CDKN1A, and CCNE2 (p ≤ 0.05) through qPCR. TiO₂ and ZnO minimized the irradiation-induced expression of genes involved in the inhibition of matrix metalloproteinases, prostanoid biosynthesis, and cell cycle pathways. Photoprotection was best observed in cell cycle-related genes, showing expression differences of up to 74% (p ≤ 0.0001). However, no distinct differences in photoprotection between TiO₂ and ZnO were found. The findings from this study serve as a framework for future optimization and development of inorganic sunscreen formulations to target genes that contribute to different aspects of skin aging.