Alleviation of photoaging‐associated <scp>MMP</scp> upregulation, prostanoid biosynthesis, and cell cycle arrest with titanium dioxide, zinc oxide, and inorganic‐only ( <scp>ZnO</scp>  +  <scp> TiO ₂ </scp> ) sunscreens

Exposure to UVR is well understood to accelerate symptoms of photoaging such as wrinkling and loss of skin elasticity. Sunscreen formulations containing titanium dioxide (TiO₂) and zinc oxide (ZnO) UV filters can therefore be used as an effective photoprotective measure to prevent the induction of signaling pathways in skin that contribute to photoaging. The aim of this study is to provide a broad investigation on the photoprotective impact of TiO₂, ZnO, and inorganic-only (ZnO + TiO₂) sunscreen formulations in human dermal fibroblasts at a gene and protein level. The study focused on genes involved in UV-only and complete solar light-induced MMP production, prostanoid biosynthesis for inflammation, and cell cycle arrest, as previously identified through RNA-seq analysis. Three inorganic formulations were prepared at commercially applicable active levels and varying particle sizes: (1) F(TiO₂ ^179nm), (2) F(ZnO^57nm), and (3) an inorganic-only (ZnO + TiO₂) formulation F(ZnO^57nm/TiO₂ ^47nm). The three formulations significantly alleviated the irradiation-induced expression of MMP1, MMP3, PTGS1, PTGES, MDM2, CDKN1A, and CCNE2, with the latter most alleviated by up to 77% (p ≤ 0.05). The inorganic-only (ZnO + TiO₂) formulation, containing both inorganic UV filters, exhibited the greatest mean or maximum alleviation in 75% of the genes investigated. Protein analyses of MMP1, PTGES, and p21, by immunocytochemistry and Western blot, also showed positive translation of alleviation at a protein level. The study provides further academic and commercial insights on the photoprotective impact of inorganic particles in sunscreens, based on relevant signaling pathways, genes, and proteins that are induced by UV to accelerate photoaging.