Cells take up and recover from protein-stabilized single-wall carbon nanotubes with two distinct rates

Single-wall carbon nanotubes (SWCNTs) are increasingly being investigated for use in biomedical applications for intracellular imaging and ablation, as well as vehicles for drug and gene delivery. One major obstacle to the development of safe, controlled, and effective SWCNT-based biomedical materials is limited quantification of dosage- and time-dependent uptake kinetics, cellular effects, and recovery profiles. Here, we quantified NIH-3T3 cellular uptake of and recovery from individualized SWCNTs dispersed using a biocompatible dispersing agent, bovine serum albumin (BSA). Uptake and recovery were determined by monitoring the mass of SWCNTs-BSA per cell, as a function of SWCNTs-BSA over the concentration range of 1 to 100 μg mL(-1) and time range of seconds to days. To determine SWCNTs-BSA biocompatibility as a function of uptake and recovery, cytotoxicity, proliferation potential, and cell phenotype were monitored for each condition. Interestingly, the rate of cellular uptake of SWCNTs-BSA was rapid, reaching steady state within ∼1 min, in agreement with modeling. We also observed a threshold SWCNT exposure level (>1 μg mL(-1)) above which internalization is saturated and uptake scales linearly with exposure amount. Cells were able to recover from SWCNTs-BSA over ∼30 h, regardless of dosage level or exposure time. We suggest that these differential rates of uptake and recovery, quantified in our work, may enable cell-based SWCNT delivery systems.