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C60-Derivatives: Applications in Electric-Field Cancer Therapy (EFCT)
We have published on the ability of highly water soluble C60-serinol (C60-ser) to be used as a transfection agent7 and the molecule’s ability to non-covalently internalize within a melanoma antibody in significant quantities without significantly affecting antibody-antigen binding8. These abilities are second to the molecule’s non-toxicity. We have also developed a C60-ser conjugate with a fluorescent label (PF-633) for intracellular tracking. This complex directly competes with unlabeled C60-ser without altering biological behavior9. Tracking the fluorescence we discovered C60-serPF can cross both cellular and nuclear membranes without producing any damage to the cell. Furthermore, C60-serPF internalizes within living cells in association with serum proteins through multiple energy-dependent pathways (not passive internalization).
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. These findings suggest C60-ser can serve as a potential delivery vehicle for therapeutic agents with intranuclear activity (DNA plasmids, drugs such as paclitaxel, gemcitabine, camptothecin, cisplatin, siRNA, transcription factors, epigenetic agents, etc.) to treat cancer. Targeted delivery of these vehicles can be achieved by their binding with tumor-specific antibodies, due to the known affinity of water-soluble fullerenes for antibodies to form immunoconjugates.
In this study, we have investigated the interactions of variable frequency EFs (10 HZ – 250 MHz) with various C60 derivatives (Figure 1) as a means of enhancing the efficacy of EFCT. We report on the enhanced toxicity of C60-Gemcitabine/Paclitaxel/Camptothecin conjugates, when used in conjunction with EFCT, as well as the intracellular distribution of fluorescently tagged (PF-633) C60-ser, as a function of EF exposure.
References
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