title: Photoluminescent carbon nanotubes interrogate the permeability of multicellular tumor spheroids.
abstract: Nanomaterials have been extensively investigated for cancer drug delivery and imaging applications. Nanoparticles that show promise in two-dimensional cell culture systems often fail in more complex environments, possibly due to the lack of penetration in dense, three-dimensional structures. Multicellular tumor spheroids are an emerging model system to investigate interactions of nanoparticles with 3Din vitrocell culture environments. Using the intrinsic near-infrared emission of semiconducting carbon nanotubes to optically reconstruct their localization within a three-dimensional volume, we resolved the relative permeability of two different multicellular tumor spheroids. Nanotube photoluminescence revealed that nanotubes rapidly internalized into MCF-7 breast cancer cell-derived spheroids, whereas they exhibited little penetration into spheroids derived from SK-136, a cell line that we developed from murine liver cancer. Characterization of the spheroids by electron microscopy and immunohistochemistry revealed large differences in the extracellular matrix and interstitial spacing, which correlated directly with nanotube penetration. This platform portends a new approach to characterize the permeability of living multicellular environments.
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.
authors.forename: Prakrit V
authors.initials: PV
authors.lastname: Jena
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.
authors.forename: Yosi
authors.initials: Y
authors.lastname: Shamay
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.
authors.forename: Janki
authors.initials: J
authors.lastname: Shah
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Roxbury
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.
authors.forename: Navid
authors.initials: N
authors.lastname: Paknejad
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.|Weill Cornell Medical College, New York, NY 10065, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Heller