Colten Watson

Nanomedicine is a relatively new application of nanotechnology. Nanoparticle are used to carrier and deliver a therapeutic payload to cancerous cells in the tissue. A fundamental issue with nanomedicine is that although the benefits have been well documented and studied, several nanoparticles in therapeutic use have been shown to induce vascular endothelial leakiness.¹² This side effect has led scientists to worry about nanomedicine use in cancer therapy; attempts have been made to determine the role of titanium dioxide, a frequently used nanoparticle which induces leakiness, in cancer metastasis. This research focused on the possible role of titanium dioxide in the development of a common metastatic neoplasm, metastatic breast cancer. Research’s hypothesized that titanium dioxide will make cancerous breast cells more susceptible to intravasation into the blood stream and extravasation into non-breast tissue. ¹ The study was designed using two different models, cultured breast cancer cell lines for molecular assays and 4-5-week-old immune-deficient female mice for transplanted tumor studies. ¹ Three independent experiments were performed to experimentally determine if titanium dioxide plays a role in cancer metastasis through the mechanism of VE-cadherin disruption, tumor intravasation, and tumor extravasation of breast cancer cells. Different concentrations of titanium dioxide and a PBS control were injected in tumor cell lines and immunodeficient mice for study. Immunofluorescent assays and histological stains of cell lines and mice were performed to determine VE-cadherin disruption and cancer cell migration due to the introduction of titanium dioxide. The 3 independent studies concluded that the titanium dioxide induces vascular endothelial leakiness in experimental breast cancer models which can facilitates metastatic breast cancer. Experimental data suggests that titanium dioxide disrupts the VE-cadherin-VE- cadherin relationship at adheren junctions in the epithelial lining of blood vessels. This interaction reduces cellular tension and creates micrometer-sized gaps (estimated to be wide enough for a cell to pass through) between closely associated vascular endothelial tissue as well as cellular adhesion to the endothelium. ^1,6,12 These micrometer-sized gaps which disrupt adheren junctions have been experimentally shown to provide a paracellular route for breast cancer cells to escape systemically into the bloodstream and eventually implant in non-breast tissue such as the lungs. Oncologists and newly diagnosed cancer patients should take this research into account when developing a treatment plan and lifestyle. The evidence presented in this research suggests that cancer patients, regardless if they have metastatic disease or not, should decrease exposure titanium dioxide which is commonly found in consumer products such as certain pharmaceuticals, toothpaste, soap, water treatment agents, sunscreen, and many more agents throughout the rest of their life. Although nanomedicine has been successful as a therapeutic agent for treating cancer, there is still inadequate epidemiologic research on the prevalence of developing metastasis while using nanomedicines in cancer treatment. ^1,6,12

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