The Role of Carbon Nanotubes in Enhancing the Effects of Chemotherapeutic Agents in Cancer Treatment Meena Mahmood 1* , Ashley Fejleh 1 , Yang Xu 1 , Enkeleda Dervishi 1 , Zhongrui Li 1 , Alexandru R. Biris 2 , Nawab Ali 3 , Ekaterina I. Galanzha 4 , Vladimir Zharov 4 , Alexandru S. Biris 1* , 1 Nanotechnology Center and Applied Science, University of Arkansas at Little Rock, Arkansas, 72204 2 National Institute for Research and Development of Isotopic and Molecular Technologies, P.O. Box 700, R-400293 Cluj-Napoca, Romania 3 Graduate Institute of Technology, Applied Science Department, University of Arkansas at Little Rock 4 Philips Classic Laser Laboratories, University of Arkansas for Medical Sciences, Little Rock, AR, 72205 * Corresponding Authors: asbiris@ualr.edu, mwmahmood@ualr.edu ABSTRACT Nanotoxicology is an important field of study that fills the knowledge gap concerning the introduction of nanomaterials into human cells, their interactions with biological systems, and the assessment of their risks to living organisms. In this study apoptosis and topoisomerase II-mediated DNA breakeages in human cervical cancer cells (HeLa cells) were effectively induced by the commonly used chemotherapeutic agent etoposide at a concentration of (75X10 -6 M) during 6 hrs of exposure. The cytotoxic effect was significantly increased by the addition of (20 μg/ml) single wall carbon nanotubes (SW- CNTs) during the incubation time. The apoptosis of the cells was observed by analyzing intracellular active caspase-3 and the DNA fragmentation by combining the nanomaterials with the Etoposide. It was found that single walled carbon nanotubes significantly increased the apoptotic efficacy of chemotherapeutic drugs such as etoposide in the treatment of malignancies. Such a combination could lead to the development of novel hybrid drugs that contain both nanostructural materials as well as apoptotic substances for the treatment of chemo resistant cancers. Keywords: cancer, carbon nanotubes, antitumor drug, combined chemotherapy. INTRODUCTION Carbon nanotubes (CNTs) with their unique physical and chemical properties hold great hopes for cancer targeting, imaging and drug delivery [1,2]. Nevertheless, besides precise targeting tumor and toxicity concerns, drug resistance remains a major obstacle for the treatment of advanced cancerous tumors. To illustrate this problem, we selected etoposide, as one of the most widely used chemotherapeutic drugs, which is a derivative of podophyllotoxin with apoptotic action, due to its ability to inhibit the topoisomerase II enzyme [3]. We propose here a new treatment strategy of cancer based on the combination of conventional drugs and nanomaterials, assuming that these nanostructures can act as bioactive molecules and promote drug action through specific interaction with the cellular structures. To verify this hypothesis, we studied the action of etoposide and CNTs on HeLa cancer cells as single and combined therapy. We observed highly increased anti-tumor activity of Etoposide-CNTs combination compared to the single administration of each agent, which suggests that the CNTs can alter the mechanisms of chemo-resistance in malign cells. We believe that this finding could lead to new treatment approaches and improvement of current cancer therapies by using both cytostatic and nanostructural materials (such as CNTs), which synergistically are more aggressive and possess greater curative rates in the treatment of cancer. NSTI-Nanotech 2009, www.nsti.org, ISBN 978-1-4398-1782-7 Vol. 1, 2009 401