Nanoparticle endocytosis is driven by monocyte phenotype rather than nanoparticle size under high shear flow...

Monocytes are members of the mononuclear phagocyte system involved in pathogen clearance and nanoparticle pharmacokinetics. Monocytes play a critical role in the development and progression of cardiovascular disease and, recently, in SARS-CoV-2 pathogenesis. While studies have investigated the effect of nanoparticle modulation on monocyte uptake, their capacity for nanoparticle clearance is poorly studied. In this study, we investigated the impact of ACE2 deficiency, frequently observed in individuals with cardiovascular complications, on monocyte nanoparticle endocytosis. Moreover, we investigated nanoparticle uptake as a function of nanoparticle size, physiological shear stress, and monocyte phenotype. Our Design of Experiment (DOE) analysis found that the THP-1 ACE2 ^- cells showed a greater preference for 100nm particles under atherosclerotic conditions than THP-1 wild-type cells. Observing how nanoparticles can modulate monocytes in the context of disease can inform precision dosing.