Preparation Of Short, Water-soluble Carbon Nanotubes And Their Application As Drug Delivery Vehicle

In the past decades, nanomaterials have been widely investigated for potential applications in biomedical field, and remarkable advances have been achieved. Carbon nanotubes (CNTs), due to their intrinsic structures and outstanding physical and chemical properties, are emerging as innovative tools in nanobiotechnology, such as imaging, tissue engineering, and cancer therapy. Particularly, CNTs have attracted considerable interest in the delivery of genes and drugs. Based on this background, this thesis focused on the preparation of multi-functional CNT-based drug delivery system, which involves the following aspects. Firstly, functionalized CNTs were prepared, which were well solubilized and stable in water, PBS, and cell medium. Secondly, mechanical shear forces were used to cut the long, entangled carbon nanotubes into short segments. Thirdly, water-soluble, multi-functionalized short multi-walled carbon nanotubes (ssMWNTs), which attached fluorescent tag and tumor-targeted molecules, have been prepared. Finally, the application of functionalized ssMWNTs as drug delivery was investigated. The main research contents and results are shown as follows:1. Water-soluble MWNTs were prepared by in situ radical polymerization of poly (ethylene glycol) acrylate (PEG-AA). The grafting amount can be controlled by the feed ratio of initiator to MWNTs and monomer to MWNTs, and the maximum grafting amount could research 20 wt%. Owing to the high hydrophilcity and good cytocompatibility of PEG, functionalized MWNTs could be well dispersed in water, and exhibited no apparent cytotoxicity in the concentration of 0-50μg/mL. Additionally, PEG side chain was ended with hydroxyl group; therefore, it is promising for further modification. 2. Rubber mastication process on a two-roller-mill was utilized to cut MWNTs into short pipes in an effective, controllable and scalable way. The relative velocity difference between the two rollers induced a strong shear force, which could break the MWNTs. The duration of treatment dominated the average length of the MWNTs. After treating for 25 minutes, the average length of the MWNTs is about 430 nm, which meets the requirement in biomedical application. In the mastication process, rubber chains undergo a mechanical rupture, leaving free radicals at the ends of ruptured chains, which could graft to the surface defects and end of MWNTs. Therefore, MWNTs were functionalized while being shortened. On the other hand, short pipes with minimum sidewall damage can be obtained by pyrolysis under N2 flow. This method can produce short MWNTs (sMWNTs) massively in a short period of time, and paves the way for further application of sMWNTs.3. Short MWNTs (sMWNTs) were functionalized with P(PEG-AA) (named as ssMWNTs), and amino groups were further introduced to the surface of CNTs based on the reaction of hydroxyl groups, then fluorescein isothiocyanate (FITC) and folic acid (FA) were additionally tethered to the ssMWNTs. Because the large surface area of CNTs is highly hydrophobic, cancer drug podophyllotoxin (PPT) were loaded to sMWNTs through hydrophobic interaction, and the loading efficiency was higher than 20%. Functionalized sMWNTs exhibited no toxicity on both 293T cells and Hela cells. PPT loaded ssMWNTs induced significant Hela cell death, and the ssMWNTs-FA-PPT showed an enhanced cell-killing effect toward Hela cells. Concentration-dependent toxicity data showed that ssMWNTs based PPT delivery systems exhibited higher toxicity than free PPT. The results above hinted that the overall nanoscale drug system is more selective and effective than the free drug and it should result in reduced side-effects in patents, and therefore holds great promise in cancer therapy.