title: Anomalously Fast Diffusion of Targeted Carbon Nanotubes in Cellular Spheroids.
abstract: 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 CNTs in highly uniform spheroids of hepatocellular carcinoma and found that apparent diffusion coefficients of CNTs in these tissue replicas are anomalously high and comparable to diffusion rates of similarly charged molecules with molecular weights 10000× lower. Moreover, diffusivity of CNTs 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 CNTs 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.
authors.affiliation: Biointerfaces Institute, University of Michigan , North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.
authors.forename: Yichun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Biointerfaces Institute, University of Michigan , North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.
authors.forename: Joong Hwan
authors.initials: JH
authors.lastname: Bahng
authors.forename: Quantong
authors.initials: Q
authors.lastname: Che
authors.forename: Jishu
authors.initials: J
authors.lastname: Han
authors.affiliation: Biointerfaces Institute, University of Michigan , North Campus Research Complex, 2800 Plymouth Road, Ann Arbor, Michigan 48109, United States.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kotov
mesh_terms: D001692:Biological Transport; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D055672:Static Electricity; D053773:Transforming Growth Factor beta1 / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D037742:Nanotubes, Carbon; D053773:Transforming Growth Factor beta1
keywords: ICC scaffolds; carbon nanotubes; diffusion; drug delivery; nanoscale drug carriers; three-dimensional cell culture