title: Internalization of C60 fullerenes into cancer cells with accumulation in the nucleus via the nuclear pore complex.
abstract: A highly water-soluble, non-ionic, and non-cytotoxic fullerene malonodiserinolamide-derivatized fullerene C(60) (C(60)-ser) is under investigation as a potential nanovector to deliver biologic and cancer drugs across biological barriers. Using laser-scanning confocal microscopy and flow cytometry, we find that PF-633 fluorophore conjugated C(60)-ser nanoparticles (C(60)-serPF) are internalized within living cancer cells in association with serum proteins through multiple energy-dependent pathways, and escape endocytotic vesicles to eventually localize and accumulate in the nucleus of the cells through the nuclear pore complex. Furthermore, in a mouse model of liver cancer, the C(60)-serPF conjugate is detected in most tissues, permeating through the altered vasculature of the tumor and the tightly-regulated blood brain barrier while evading the reticulo-endothelial system.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA. mraoof@mdanderson.org
authors.forename: Mustafa
authors.initials: M
authors.lastname: Raoof
authors.forename: Yuri
authors.initials: Y
authors.lastname: Mackeyev
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cheney
authors.forename: Lon J
authors.initials: LJ
authors.lastname: Wilson
authors.forename: Steven A
authors.initials: SA
authors.lastname: Curley
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004705:Endocytosis; D037741:Fullerenes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles; D022022:Nuclear Pore / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D037741:Fullerenes; D008055:Lipids; C069837:fullerene C60