Carbon Nanotubes in Cancer Therapy

Abdallah, Banu (2013) Carbon Nanotubes in Cancer Therapy. Doctoral thesis, University of Central Lancashire.

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Carbon Nanotubes (CNTs) are highly attractive vehicles for the delivery of bio-molecules into living systems specifically for applications in cancer therapy. Two main types of CNTs; single-walled (SWNT) and multi-walled (MWNT) have been investigated. Pristine CNTs are poorly soluble in aqueous solvents, and therefore need to be functionalized (f-CNT) to enhance their solubility and biocompatibility. The f-CNTs possess the ability to cross cell membranes and enter cells consequently having the potential as vehicles for drug delivery. Polyethylene glycol (PEG400) and Pluronic®F127 (PF127) functionalized SWNTs and MWNTs have been investigated in this study for in vitro cancer therapy. Both have demonstrated high tumour suppression efficacy with respect to an anti-cancer drug Paclitaxel, when utilised solely. However, f-CNTs for the delivery of anti-cancer agents for brain tumours, in particular the most common tumour Glioblastoma, have not been researched. The toxicity of these materials is another issue that requires further investigation. Cytotoxicity of CNTs is thought to be dependent on several characteristics such as length, purity and type of functionalization.
The aim of this study was to characterize, functionalize and investigate in vitro cell cytotoxicity of f-CNTs with and without Paclitaxel (PTX). As dispersing and stabilization agents two polymeric systems were used; PEG400 and PF127. CNTs characteristics have been investigated by using various techniques and two stabilization and dispersing agents have been used for functionalization.
Raman spectra have been recorded using two laser lines at 325 nm and 488 nm. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were used to analyse their structure and morphology. All samples were functionalized, homogenised, centrifuged and their ζ-potentials were measured. CNTs were found to be in a size range of 100 nm to several microns long, with diameter values ranging from 07 ± 1.0 nm for SWNT and inner diameter I.D. 10-20 nm and 30-40 nm Outer Diameter values (O.D.) with 6-12 concentric walls for MWNT. Both SWNT and MWNT exhibited stability in both polymeric systems implemented even after a 10 day period. Particularly PEG400 based formulations showed superior performance in terms of greater ζ-potential values. Notable shifts in G-band were examined confirming the presence of f-CNTs. Higher entrapment efficiency was accomplished with f-CNTs reaching a maximum efficiency at 200 μg/ml.
Cell lines SVGp12 and U87-MG were exploited for cytotoxicity evaluations. SWNT and MWNT demonstrated insignificant cytotoxic effects on SVGp12 (normal astrocytes) cell lines even at elevated concentrations of up to 15 mg/ml. Nevertheless, f-CNTs showed significant reduction in the cell viability at low Paclitaxel concentrations on U87-MG grade IV Glioblastoma. As a selection of CNTs have been investigated by various researchers, it is exceptionally challenging to conclusively state whether or not they are indeed toxic.
This research into CNTs has successfully examined the effects of co-formulation with various components and the potential effects on drug delivery for cancer cells. Conceptually, CNTs are rightfully labelled as the king of nanomaterials due to their elusive chemical and physical properties; ensure that they are likely to receive much attention in the not too distant future.

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