Nanotechnology-Based Precision Tools for the Detection and Treatment of Cancer by Chad A. Mirkin Thomas J. Meade Sarah Hurst Petrosko & Alexander H. Stegh

Author:Chad A. Mirkin, Thomas J. Meade, Sarah Hurst Petrosko & Alexander H. Stegh
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

3.3 Cell Cycle

Using the prostate carcinoma cell line DU-145, Roa and others have documented changes in cell cycle distribution following treatment with ~10 nm gold nanoparticles coated with 6-deoxy-6-fluoro-1-thio-D-glucose [52]. As in most other studies, gold nanoparticles were found in cytoplasmic vesicles and it is difficult to decide which exact mechanism is responsible for cell cycle perturbation after nanoparticle treatment. Inhibition of glucose uptake by cytochalasin B and with it, inhibition of uptake of glucose-coated nanoparticles partially reversed the nanoparticle effects. Cell cycle perturbations were most noticeable in G2/M phase of cell cycle during which cells are the most radiation sensitive. It is, therefore, very possible that the increase in radiosensitivity noted in nanoparticle treated cells could be associated with cell cycle perturbations, especially when one considers that nanoparticles never came closer than 6 nm from the nuclear DNA.

Increased number of cells in G2/M phase of cell cycle was noted also in glioblastoma cells (SNB-19 and U87MG) in culture after treatment with titanium dioxide nanotubes [38]. Moreover, in this study it was noted that the DNA repair was reduced in glioblastoma cell lines after they engulfed TiO2 nanorods (approximately 10 nm in diameter and up to 500 nm long). As nanorods remained in vesicles inside the cytoplasm in these cells, actual mechanism(s) responsible for these changes in cellular homeostasis are as of yet unclear. Increased numbers and persistence of DNA DSBs indicated by gamma H2AX foci (specifically in nanorods treated and irradiated cells) described in this study is similar to findings of others with other types of nanomaterials (e.g. [19, 20, 43, 69]). Many possible avenues for speculations about decrease of DNA repair in this work can be envisioned. Interaction of these nanoconstructs with the proteasome, for example, is quite possible considering that TiO2 nanorods of 6 and 20 nm alter proteasomal activity [6], which, in turn, regulates DNA repair (e.g. [35]).

Perturbation of cell cycle by nanomaterials, however, does not always lead to increased numbers of cells in G2/M phase of the cell cycle. On the contrary, Mackey and El-Sayed used 30 and 15 nm gold nanoparticles (suitable for plasmon resonance and conjugated with nucleus targeting and cytoplasm-targeting peptides) in human oral squamous carcinoma cells (HSC-3) and found an accumulation of cells in the S phase with a depletion of cells in the G2/M phase [32]. These particles were not used for radiosenitization (where they could even have caused increased radioresistance); they have been tested in combination with 5-fluorouracil. Because this chemotherapeutic drug kills the cells in S phase most effectively (unlike ionizing radiation), drug and nanoparticle use had synergistic effects in this study.

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