Decoding membrane- versus receptor-mediated delivery of single-walled carbon nanotubes into macrophages using modifications of nanotube surface coatings and cell activity

Abstract

Therapeutic applications of single-walled carbon nanotubes (SWCNTs) require understanding uptake mechanisms in macrophages, which are involved with many physiological and pathological processes. However, therapeutic applications are limited by poor quantification and mechanistic understanding of uptake into macrophages with different levels of activation. We find delivery of more than 50 million SWCNTs per cell to activated macrophages, which is 10× more than unactivated macrophages and 100× more than fibroblasts. Determining the mechanisms of SWCNT uptake is important for tuning this specific delivery, but standard cellular assays are inapplicable with SWCNTs, which quench fluorescence. By modification of surface coatings on the SWCNTs and altering macrophage activation, we applied models of macrophage uptake of SWCNTs and quantified precise model parameters. With this model, we show receptor-mediated processes saturate, and above the saturation levels we observe little added delivery as well as a reduction in cell proliferation and visibly altered cell morphology. Thus, SWCNTs can be preferentially delivered to activated macrophages, and the model of uptake suggests delivery is optimized between high extracellular levels and receptor saturation.