Water-dispersible Magnetic Carbon Nanotubes And Their Properties As MRI Contrast Agents

In recent years, carbon nanotubes (CNTs) have emerged as a leading nanomaterial for biomedical applications due to their extraordinary properties. However, unmodified CNTs tend to aggregate due to their hydrophobicity and thus are difficult to disperse or solubilize in aqueous solutions, which may limit their potential applications. Surface modifications of CNTs are therefore necessary for improving their dispersion in aqueous environments, making them potentially useful for biomedical applications. The use of CNTs as potential Magnetic resonance imaging (MRI) contrast agents is one of biomedical applications that a number of research groups have focused on. The combination of polymer modified CNTs (as carriers) and attached metal ions (as contrast components) is expected to be highly suitable for use as MRI contrast agents with improved efficiency, dispersibility, and biocompatibility. The choices of efficient polyelectrolyte and suitable method to load magnetic particles on the CNTs have been investigated, and the main results are summarized as follows:Poly(diallyldimethylammonium chloride)(PDDA) was coated on the surface of acid treated MWCNTs via electrostatic interactions and superparamagnetic iron oxide (SPIO) nanoparticles modified with a potential targeting agent, lactose-glycine adduct (Lac-Gly), were subsequently immobilized on the surface of the PDDA-MWCNTs. A narrow magnetic hysteresis loop indicated that the product displayed superparamagnetism at room temperature which was further confirmed by ZFC (zero field cooling)/FC (field cooling) curves measured by SQUID. The multifunctional MWCNT-based magnetic nanocomposites showed low cytotoxicity in vitro to HEK293and Huh7cell lines. Enhanced R2relaxivities were observed for the hybrid material (186mm-1s-1) in comparison with the pure magnetic nanoparticles (92mm-1s-1) due to the capacity of the MWCNTs to "carry" more nanoparticles as clusters. More importantly, after administration of the composite material to an in vivo liver cancer model in mice, a significant increase in tumor to liver contrast ratio (277%) was observed in T2weighted magnetic resonance images.Diblock copolymers containing poly[2-(methacryloyloxy) ethyl trimethyl ammonium chloride](PMETAC), a positively charged block, and poly[(ethylene glycol) methacrylate](PEGMA) neutral block with tailored molecular weight and low polydispersity, were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Acid treated MWCNTs were coated with the RAFT diblock copolymers to improve their dispersibility in aqueous phosphate buffered saline (PBS) solution. The short positively charged PMETAC block was designed to attach the block copolymer to the surface of MWCNTs via the electrostatic interaction while the PEGMA block improved the aqueous dispersibility of MWCNTs. Extensive screening of the diblock copolymers with different degree of polymerization (DP) showed that the PBS dispersion stability of polymer-coated MWCNTs was greatly improved with the increased chain length of the PEGMA block. In particular, the MWCNTs coated with a diblock copolymer containing PEGMA (DP=118, the longest block investigated) showed a super dispersion stability in both water and PBS solution.Fe3O4nanoparticles were synthesized in situ inside the tube of MWCNTs pre-treated by a mixture of strong acids under assistance of microwave. The Fe3O4-CNT hybrid materials were subsequently coated with different length of diblock copolymers prepared by RAFT polymerization via electrostatic interaction resulting in improved PBS dispersion stability (over7days). A narrow magnetic hysteresis loop indicated that the product possessed superparamagnetism at room temperature which was further confirmed by ZFC/FC curves measured by SQUID. The multifunctional MWCNT-based magnetic nanocomposites showed low in vitro cytotoxicity to CHO-GFP and Huh7cells. In vitro T2relaxivity of the prepared hybrid materials decreased with increasing PEGMA block length. Acute tolerance testing in mice showed a high tolerant dose of greater than100mg kg-1to the CNT hybrid as the mice showed no adverse responses for5days following treatment. Most importantly, after administration of the composite, a significant increase in tumour to liver contrast ratio was observed in in vivo MRI tests.