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Internalization of C60 fullerenes into cancer cells with accumulation in the nucleus via the nuclear pore complex

2012; Elsevier BV; Volume: 33; Issue: 10 Linguagem: Inglês

10.1016/j.biomaterials.2011.12.043

1878-5905

Mustafa Raoof, Yuri Mackeyev, Matthew Cheney, Lon J. Wilson, Steven A. Curley,

Graphene and Nanomaterials Applications

A highly water-soluble, non-ionic, and non-cytotoxic fullerene malonodiserinolamide-derivatized fullerene C60 (C60-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 C60-ser nanoparticles (C60-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 C60-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.