Sunscreens protect skin against sunburn. However, studies have demonstrated that UV-irradiated sunscreen components such as titanium dioxide (TiO₂) promote the photogeneration of reactive oxygen species (ROS). Because encapsulation of TiO₂ within zeolites alters its photocatalytic activity, supramolecular composites based on NaY zeolite hosts containing TiO₂ guests were prepared, and the effects on ROS formation in cells under UVA-irradiation evaluated. DCFH-DA (2′,7′-dichlorofluorescein diacetate) was used as a profluorescent probe to monitor intracellular ROS. The detection of intracellular 2′,7′-dichlorofluorescein (DCF) fluorescence by confocal microscopy revealed that DCFH-DA was taken up, hydrolyzed and oxidized by yeast cells and cultured human skin fibroblasts within 20 and 6 min, respectively. Higher DCF fluorescence was observed in fibroblasts following UVA irradiation in the absence but not in the presence of the radical nitroxide, TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl), which exhibits superoxide dismutase-mimetic and catalase-mimetic activity. UVA-induced fluorescence increased by ∼50% in the presence of 32-nm anatase TiO₂ particles and decreased by essentially an equal amount in the presence of TiO₂ encapsulated within NaY zeolites (TiO₂@NaY). Addition of the uncomplexed NaY host also decreased (by ∼30%) the amount of UVA-induced fluorescence but, unexpectedly, the combination of the free guest and host (TiO₂ NaY) caused a doubling of the fluorescence. Protection of cells against TiO₂-induced intracellular ROS by encapsulation suggests that supramolecular species may be beneficial in photoprotection of the skin. In contrast, the potentiation of TiO₂-induced ROS by uncomplexed NaY points to a critical role for formulation when free TiO₂ is used as a sun screen ingredient.