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 approximately 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 approximately 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.