Study On The Cytotoxicity, Functionalization Of Single Walled Carbon Nanotubes And Their Applications As Nanovectors For Targeted Drug Delivery

Carbon nanotubes (CNTs) are seamless cylinders rolled up by grapheme sheets, which could be divided into single walled carbon nanotubes (SWNTs) or multi-walled carbon nanotubes (MWNTs) depending on the number of the grapheme layers. Due to their unique electrical, physical and chemical properties, CNTs have attracted tremendous interests in numerous fields such as sensors, field-effect-emitter and hydrogen storage. Most recently, CNTs have been intensively explored as nanovectors for targeted drug delivery and focused on 1) the biofunction alization and cytotoxicity of CNTs; 2) Design, preparation and evaluation of CNTs based drug delivery system. In this work, we used several natural polysaccharides to functionalize CNTs and quantitatively evaluated the effect of length, diameter, concentration and functional group of the polysacchrides on the cytotoxicity of CNTs. Furthermore, a targeted drug delivery system based on CNTs was prepared and investigated both in vitro and in vivo in terms of efficiency and side effects. The details are as follows:1) Quantitatively investigating the effect of length, diameter, concentration and functional group on the cytotoxicity of CNTs. The experimental results reveal that 1) the cytotoxicity of CNTs are dose- and size-dependent. CNTs with larger concentration or smaller diameter are more toxic; 2) The cytotoxicity of CNTs was greatly effected by the types and charge properties of the functional groups. The CNTs gain better biocompatibility only when functionalized by amylose simultaneously bearing hydroxyl group and neutral surface charge. 3) Cut CNTs are easy to penetrate cell membranes and residue in lysosomals, which is independent of the diameters and polysaccharides functionalization.2) Prepared a targeted drug delivery system (DDS) by attaching folic acid and doxorubicin to CHI wrapped SWNTs. It was found that the DOX was loaded at a high ratio and only released at acidic environment (e.g. pH= 5.5) while remain stable in the physiological envronment (pH= 7.4). The in vitro results show that the DDS was superior to free DOX due to its controlled release and targeted delivery of DOX.3) The in vivo performance of the DDS was further investigated using nude mice bearing SMMC-7721 tumor as the animal model. The DDS was i.v. administrated into the mice which were sacrificed three weeks later for biochemical and histological examinations, during which the body weights and tumor volumes were recorded. It was demonstrated that, when at the equivalent DOX dose, the DDS was more efficient than free DOX in inhibiting the growth of tumors while caused less side effects.