 The study investigates four different endocytotic uptake mechanisms, including phagocytosis, macropinocytosis, clathrin, and cavelin-mediated endocytosis, in mouse macrophages, J774A1, and human alveolar epithelial type 2 cells, A549. The study uses fluorescently tagged marker proteins to determine the involved pathway in nanoparticle uptake by optimizing specific inhibitors for each endocytotic pathway. The results show that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role in the uptake of 40 nanometers polystyrene nanoparticles in both cell lines. Additionally, cavelin-mediated endocytosis is involved in the uptake of nanoparticles in A549 cells, while clathrin-coated vesicles are required for clathrin-mediated endocytosis in both cell lines. Overall, the study suggests that a combination of several distinguishable endocytotic uptake mechanisms is involved in the uptake of nanoparticles in both macrophages and epithelial cells.