Cell-Nanomaterial Interaction: Implications in Cell-Signaling and Targeted Therapy

R. Kudgus
Mayo Clinic, US

Summary:

Biomedical nanotechnology is an evolving field having enormous potentials to positively impact health care system. Important biomedical applications of nanotechnology that may have potential clinical applications include targeted drug delivery, detection/diagnosis and imaging. However, basic understanding of how nanomaterials interact with the cells is not properly investigated. Probing cell-nanomaterial interaction may be a unique way to discover new signaling events in cancer. Thus, another potential biological application that has not been explored so far is the use of nanotechnology as a powerful tool to discover new cell-signaling pathways. Recently, we have demonstrated that the positively charged gold Nanoparticles (+AuNPs) depolarize the membrane potentials of both normal (bronchial epithelial and airway smooth muscle cells) and malignant cells (ovarian cancer cells). Such membrane depolarization leads to an influx of extracellular calcium into the cytosol through L-type channels with a subsequent increase in intracellular calcium [Ca+2]i from 100 nm to ~ 800 nm in both normal as well as cancer cells. Increase in [Ca+2]I leads to the inhibition of proliferation and induction of apoptosis of normal BECs and ASMs, whereas cancer cells remain unaffected. These findings clearly suggest that cancer cells has unique ability to evade [Ca+2]i induced cell death and inhibition of proliferation. Delineating such mechanisms will help to indentify new therapeutic targets to sensitize cancer cells towards apoptosis or anti-proliferative effects. Using surface engineered nanoparticles, in this talk, we will explore the mechanisms of resistance of cancer cells, ovarian cancer cells in particular, to [Ca+2]i induced inhibition of proliferation. Such investigation may lead to the discovery of new therapeutic targets that will have a long-term impact in the management ovarian cancer.