Single-Wall Carbon Nanotube Uptake Based on Energy-Dependence and Metastatic Potential of Epithelial Cells Motivates Carrier Delivery of Drugs for Targeting Cancer

Abstract

Cancer cells have altered metabolic activity that can be appropriated for delivery of drugs. Rapidly proliferating cancer cells internalize a high amount of protein-dispersed single-wall carbon nanotubes (SWCNTs) with increased endocytosis from deprivation of metabolic fuels, overexpression and increased recycling of membrane receptors, and mechanosensitivity. Differential uptake of protein-dispersed SWCNTs in various cell types have been reported previously, demonstrating that SWCNT uptake highly depends on uptake pathway and cell metabolism. However, there is still gap in understanding how metastatic potential and cell metabolism can differentiate SWCNT uptake and delivery of drugs in a type of cells. In this work, we present uptake and efficacy of SWCNTs/drug/protein complexes in three different epithelial cell lines, NRK-52E, HeLa, and Hs 578T, that present different metabolic levels from their metastatic potentials. We first create SWCNTs/drug/protein complexes with doxorubicin, a common model cancer drug, and bovine serum albumin (BSA), a model protein that has been extensively studied with SWCNT, using a previously developed unique drug loading system using stepwise assembly on SWCNT networks. The result presented that the cells takes up SWCNTs differently in accordance to their metabolic activity, where Hs 578T cells, with the highest metastatic potential and metabolism, take up ~ 10× more nanotubes compared to an epithelial monolayer of NRK-52E cells. Extent of reduction in cell viability from the delivered drugs were in line with the amount of SWCNT uptake. Our work provides further understanding of differential uptake of protein-dispersed SWCNTs with respect to metabolism and energy requirement of the cells. This suggests that protein-dispersed SWCNTs could preferentially target and deliver drugs to cancer cells in a local area with a combination of normal epithelial cells and cancerous cells.