Length-Dependent Uptake, Inflammation, and Intracellular Processing of Single-Wall Carbon Nanotubes in Macrophages

Abstract

Understanding the impact of single-wall carbon nanotube (SWCNT) lengths on cytotoxicity, uptake and intracellular processing is essential in realizing SWCNT-based drug delivery systems. In addition, cell type-specific response to SWCNT cannot be neglected since SWCNT uptake and processing vary across different cell types. Immune cell-specific processing of SWCNTs in different lengths is of particular interest because immune cells are capable of two distinct size-dependent cellular entry pathways; endocytosis and phagocytosis, and they engage in various physiological conditions such as wound healing, inflammation, and cancer. In this work, we present the impact of SWCNT lengths on uptake, inflammation, and intracellular processing of SWCNTs in macrophages. SWCNTs with average lengths of 50 nm (ultra-short), 145 nm (short), and 500 nm (long) were noncovalently dispersed with bovine serum albumin (BSA), which promotes cellular uptake without affecting cell viability. Interestingly, the amount of uptake was significantly higher for ultra-short SWCNTs compared to longer nanotubes. Moreover, short-SWCNTs became highly bundled in macrophages, which were mostly retained for at least 24 h. In contrast, most long- and ultra-short- SWCNTs remained individualized inside macrophages and were eventually exocytosed over time. Further, we observed pro-inflammatory behavior of macrophage upon exposure to ultra-short-SWCNTs. Overall, the length-dependent inflammation and intracellular processing in macrophages allow for tailoring SWCNT properties for biomedical therapy and imaging. High internalization and subsequent exocytosis of ultra-short-SWCNTs and the triggered pro-inflammatory behavior are more preferred for cancer therapy and drug delivery, while high retention of short-SWCNTs in macrophages could be more desirable for biomedical imaging and macrophage tracking in vivo.