Aug 1, 2014
Carbon nanomaterials: sensitizing cancer cells to chemotherapeutics
Carbon nanomaterials, such as carbon nanofibers (CNFs) and multi-walled carbon nanotubes (CNTs), exert anti-tumour activity. They also sensitize cancer cells to conventional chemotherapeutics such as carboplatin (CP) and cisplatin (CDDP). Simultaneously administering chemotherapeutics with carbon nanomaterials could reduce the dose required and minimise severe side effects and chemoresistance. Reporting in Nanotechnology, the enhanced cell apoptosis and inhibition of cell proliferation were identified as underlying mechanisms of the chemosensitizing effect of CNFs and CNTs.
Enhanced apoptosis of DU‑145 prostate cancer cells following combinatory treatment with carbon nanomaterials and chemotherapeutics.
The platinum-based chemotherapeutics CP and CDDP are effective against different types of cancer. However, their administration is often limited by the development of chemoresistance – or the resistance of cells to certain chemicals – which can arise from various reasons such as the inhibition of apoptosis. Recent evidence suggests that CNFs and CNTs can sensitize cancer cells to conventional chemotherapeutics.
Understanding the chemosensitizing effect
The team from the Technische Universität Dresden and the Leibniz Institute of Solid State and Material Research have previously demonstrated the combinatory treatment of bladder and prostate cancer cells with carbon nanomaterials and CP or CDDP. This results in a markedly increased inhibition of cellular viability. Now, they use different experimental approaches to evaluate the underlying mechanisms of this chemosensitizing effect.
Apoptosis not necrosis
Depending on the cell line, the simultaneous administration of chemotherapeutics and carbon nanomaterials produces an additional inhibition of cellular proliferation and clonogenic survival of up to 77% and 98% respectively. This is in comparison to the inhibitory effects of the chemotherapeutics alone. These strongly enhanced anti-proliferative effects are accompanied by an elevated cell death rate, which is predominantly mediated via apoptosis and not by necrosis.
The enhanced effects of the combinatory treatments on cellular function are mostly of the additive to the partly synergistic nature. Furthermore, the cell cycle analysis demonstrates an arrest at the G2/M phase which is mostly mediated by the chemotherapeutics and not the carbon nanomaterials. This suggests that the pronounced chemosensitizing effects of CNFs and CNTs are mediated by an enhanced apoptosis and inhibition of proliferation.
Cell death rate of cancer cells following treatment with carbon nanomaterials and chemotherapeutics alone or in combination.
The results present a valuable basis for detailed animal studies addressing the toxicity and anticancer effects of carbon nanomaterials in combination with conventional chemotherapeutics in vivo. Ultimately, prostate and bladder cancer present potential targets for the local administration of carbon nanomaterials-based therapies due to their good accessibility from outside the body.
More information about the research can be found in the journal Nanotechnology 25 405102.
Mesoporous silica nanocomposite simplifies combination therapy (June 2014)
Chitosan provides skeleton for anticancer pro-drug (June 2014)
Carbon nanotubes increase clinical breast imaging efficiency (May 2014)
About the author
Kati Erdmann works in the research laboratory of the Department of Urology, Technische Universität Dresden. Ongoing research projects of the group are focused on the improvement of diagnosis and prognosis of urological cancers as well as on the evaluation of innovative biomedical applications such as carbon nanomaterials suitable for cancer treatments. The present study was supported by the German Cancer Aid (grant number 109616) and conducted in close cooperation with the Leibniz Institute of Solid State and Material Research/Germany.