Synthesis Of Magnetic Iron Oxide Nanoparticles With Water-Soluble Polymer Ligands And Their Bio-Applications

Magnetic nanoparticles (NPs) have gained much scientific interest for their unique magnetic properties such as superparamagnetism. high coercivity. low Curie temperature, and high magnetic susceptibility. Magnetic iron oxide nanoparticles (MIONs). owing to their advantages such as low toxicity and biocompatibility are considered to be the most favorable candidates for bio-applications including magnetic resonance imaging (MRI). magnetic fluid hyperthermia (MFH), magnetic separation and immobilization of biomolecules such as nucleic acids and proteins, the development of drug delivery systems for controlled release of drugs biolabeling and magnetic sensors. Thermal decomposition and co-precipitation are among the most common techniques employed for MIONs preparation owning to their advantages but these are still associated with some limitations. Thermal decomposition method involves the pyrolysis of organic iron salts at high temperatures in organic solvents and subsequent oxidation which results in the preparation of highly monodisperse iron oxide NPs with high monodispersity. crystallization and large saturation magnetization. However, these NPs are water-insoluble and require post-synthesis ligand exchange procedures for bio-applications. Co-precipitation method, on the other hand, yields magnetic NPs. which are directly dispersed in aqueous phase and are feasible for bio-applications. Unlike thermal decomposition method, it does not employ the use of high temperature and expensive organic metal precursors and solvents. Moreover, since physico-chemical properties of magnetic NPs depend on their size and shape, the development of new protocols for synthesis non-aggregated NPs with a well controlled mean size and a narrow size distribution is essential. A vital aspect in the NPs synthesis procedure is its capability to keep them physically apart and prevent irreversible agglomeration. Different types of protective molecules or capping ligands are employed for this purpose which bind to the NPs surface and avoid their aggregation in aqueous solution. Therefore it is necessary to develop some easy and efficient method for preparation of MIONs with better control over size and magnetic properties. Multifunctional water-soluble polymers as capping ligands can play an important role in the preparation of MIONs and other inorganic NPs. In aqueous co-precipitation process, polymer ligands can efficiently tune the size and shape of the NPs due to the presence of abundant functional groups such as-COOH.-OH.-SH and-NH:etc. These multifunctional polymers render magnetic NPs more stable, water-soluble and uniform in addition to providing them rich surface chemistry which opens up ways for easier post-synthesis modification and functionalization for bio-applications. Numerous studies have been reported for the synthesis of MIONs using polymer ligands in order to render them water-soluble and biocompatible. However, in most of the cases, the NPs are first prepared through thermal decomposition and then made water-soluble through post-synthesis modification processes such as ligand exchange using water-soluble polymer ligands.In this thesis we have reported simple synthesis of highly water-soluble and ultrasmall (4-10nm) MIONs using thiol and thioether end-functionalized multifunctional water-soluble polymer ligands such as dodecanethiol-polymethacrylic acid (DDT-PMAA). pentaerythritoltetrakis (3-mercaptopropionate)-polymethacrylic acid (PTMP-PMAA). PTMP-polyA-vinyl-2-pyrrolidone (PTMP-PVP) etc. Effect of the concentration and molecular weight of polymer on the size and magnetic properties of the MIONs was also studied. High temperature single step co-precipitation method was developed and modified in order to prepare uniform MIONs with optimum size and magnetic properties for bioapplications. MIONs prepared using DDT-PMAA and PTMP-PMAA have several carboxylic acid (-COOH) functional groups which provide them excellent solubility and stability in aqueous solutions.These MIONs showed high resistance against aggregation in aqueous media over a wide range of pH and salt concentration due to excellent electrostatic and steric stabilization provided by the polymer ligand. These MIONs can be dried by evaporating solvent and stored as powder for several months without any undesired changes in their chemical and physical properties. The polymer ligand offers MIONs better chemical stability against oxidation which otherwise leads to a decrease in their magnetic properties. Furthermore, cytotoxicity analysis of the MIONs proved them to be biocompatible even at their high concentration up to500μg mLBio-applicability of MIONs prepared with DDT-PMAA was demonstrated by their conjugation with an anti-cancer drug doxorubicin and studying the efficacy of these drug-NP conjugates by incubating them with HepG2cells, through MTT-assay. These drug-NP conjugates were found to have a better anti-cancer drug activity compared to the free drug. The improved drug activity in case of drug-NP conjugates may be due to active NPs cellular uptake through endocytosis compared to the simple diffusion in case of free drug.Similarly, poly N-vinyl-2-pyrrolidone (PVP) is an important water-soluble polymer ligand, which has been widely used as stabilizer for synthesis of inorganic NPs. PVP has2-pyrrolidone unit in its polymer chain back-bone which, due to its high polarity, has ability to effectively coordinate with iron oxide NPs surface. The MIONs obtained with PTMP-PVP had small size and narrow size distribution, and were found to be extremely bio-compatible as determined through MTT-assay. therefore are supposed to be good candidates for several bio-applications such as contrast agents for MRI which was demonstrated through in vitro experiments. Magnetic iron oxide nanoparticles prepared with PTMP-PVP were found to have potential as positive and negative dual contrast agents for magnetic resonance imaging (MRI) as determined through in vitro experiments.Finally, it is concluded that MIONs stabilized with multifunctional water-solublc polymer ligands were extremely biocompatible and have large scope of bio-applications such as magnetic separation. drug delivery and bio-imaging owing to their chemically rich surface providing numerous opportunities for their conjugation with a variety of therapeutic, targeting, and labeling agents.