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.