Effects of nanoparticles on cell apoptosis: potentials and limits for cancer therapy

The goals of nanomedical strategies for effective cancer therapies are: 1) to deliver an effective dose of an anticancer drug directly to cancer cells, 2) to enhance apoptosis of cancer cells, and 3) to minimize healthy tissue damage. These strategies need efficacious and safe nanoparticles as drug delivery carrier or drug enhancer. The goal of my PhD was to understand the mechanisms by which nanoparticles (NPs) interfere with cell apoptotic signaling in order to highlight limits and potentials of NPs exploitation in cancer treatments. We evaluated two classes of NPs: 1) shuttle NPs: multi-wall carbon nanotubes (MWCNT) or dextran; 2) NPs where the material itself is an active agent: CeO2 nanoparticles. The studies of the interactions of these NPs with cells revealed: a) that MWCNT induce maturation and demise of human primary monocytes; b) that irradiated CeO2 nanoparticles, via their Ce3+/Ce4+ redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer; c) that CeO2 nanoparticles may hinder anti-cancer therapy in leukemia cells; d) that dextran-etoposide conjugates, able to slowly release the active drug so as to shift cytotoxic to metronomic therapy, may be a novel tool for dosage control in anticancer reprogramming therapy. These results confirm that nanotechnology applied to biology/medicine may act as a double-edged sword, because on the one hand it offers tremendous opportunities to cancer therapy, but on the other hand it can be a potential threat to human health.