Wang Y, Bahng JH, Che Q, Han J, Kotov NA.
Biointerfaces Institute, University of Michigan , North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.
Understanding transport of carbon nanotubes (CNTs) and other nanocarriers within tissues is essential for biomedical imaging and drug delivery using these carriers. Compared to traditional cell cultures in animal studies, three-dimensional tissue replicas approach the complexity of the actual organs and enable high temporal and spatial resolution of the carrier permeation. We investigated diffusional transport of carbon nanotubes in highly uniform spheroids of hepatocellular carcinoma and found that apparent diffusion coefficients of carbon nanotubes in these tissue replicas are anomalously high and comparable to diffusion rates of similarly charged molecules with molecular weights 10000× lower. Moreover, diffusivity of carbon nanotubes in tissues is enhanced after functionalization with transforming growth factor β1. This unexpected trend contradicts predictions of the Stokes-Einstein equation and previously obtained empirical dependences of diffusivity on molecular mass for permeants in gas, liquid, solid or gel. It is attributed to the planar diffusion(gliding) of carbon nanotubes along cellular membranes reducing effective dimensionality of diffusional space. These findings indicate that nanotubes and potentially similar nanostructures are capable of fast and deep permeation into the tissue, which is often difficult to realize with anticancer agents.Go To ACS Nano.