J.C.K. Lai, V. Desai, Y. Zhang, A. Bhushan, S. Leung
Idaho State University College of Pharmacy,
Keywords: cytotoxic effects, short multi-wall carbon nanotubes, funationalized carbon nanotubes, pancreatic cancer PANC-1 cells
Summary:Extensive recent research in structure and function of carbon nanotubes (CNTs) has elucidated the unique physico-chemical properties of CNTs. Increasingly diverse industrial and biomedical applications of CNTs have exploited their unique properties to some advantage. Such applications include, but are not limited to, fabrications of transistors, capacitors, actuators, electrodes, catalysts, and sensors. Their ubiquity in numerous and diverse industries suggests humans are likely to be increasingly exposed to CNTs. Nonetheless, the health hazard of exposing humans to CNTs is as yet poorly understood. We have developed a variety of cell models in vitro to allow us to launch a series of studies to systematically investigate the putative cytotoxicity of a variety of nanomaterials, including CNTs, on many tumor as well as normal cell types. Consequently, employing these models we have been able to make significant advances in understanding the molecular mechanisms underlying the putative cytotoxic effects of a variety of nanomaterials, especially nanoparticles and CNTs. Our recent studies of the cytotoxic effects of nanoparticles on several neurotumor cell types, including astrocytoma and neuroblastoma, prompted us to propose that the nanoparticles’ cytotoxic effects on cancer cells could be gainfully exploited when the nanoparticles are employed to deliver anti-cancer drugs to target tumors. Because CNTs have only been minimally studied in this context compared to nanoparticles, we have focused this study on the putative cytotoxic effects of short multi-wall carbon nanotubes (SMWCNTs) on pancreatic cancer cells. Because pancreatic cancer is an aggressive form of cancer with poor prognosis and very low five-year survival rate and chemotherapeutic and radiation treatments are ineffective, there is an urgent need for new and/or improved treatment for this deadly cancer. Based on their unique properties, CNTs have been examined for their potential as drug delivery vehicles and diagnostic agents. Modification of CNTs with functional groups improves solubility/dispersibility and may serve as attachment site of other molecules and/or drugs. Nonetheless, the putative cytotoxic effects of functionalized and non-functionalized CNTs on pancreatic cancer cells have not been systematically investigated. This study was initiated to examine the effects of functionalized (namely carboxylated (SMWCNTs-COOH)) and non-functionalized SMWCNTs on pancreatic cancer PANC-1 cells. Employing modified cell survival assays, our findings demonstrated that exposure of PANC-1 cells to functionalized (SMWCNTs-COOH) and non-functionalized SMWCNTs induced dose- and time-related decreases in their survival, the non-functionalized SMWCNTs being more cytotoxic than the functionalized SMWCNTs-COOH to the PANC-1 cells. Our flow-cytometric studies also revealed that while both functionalized and non-functionalized SMWCNTs induced apoptosis in PANC-1 cells, the non-functionalized SMWCNTs exerted more pronounced apoptotic effects on these cells compared to the SMWCNTs-COOH. Taken together, our results strongly suggest functionalized and non-functionalized SMWCNTs induced differential cytotoxic effects on PANC-1 pancreatic cancer cells. Thus, our findings may have pathophysiological implications in the biocompatibility and health hazard of carbon nanotubes. Furthermore, our results also suggest that the cytotoxic effects of carbon nanotubes could be productively exploited in designing new drug delivery systems to treat this deadly cancer.