| With the development of nanoscience and nanotechnology, nanoscale platforms lead a new direction in the biomedical field, especially in the clinical aspect of the contrast agents. Currently, superparamagnetic iron oxide(Fe3O4) nanoparticles(NPs) and gold(Au) NPs have been widely used in the field of magnetic resonance(MR) imaging and computed tomography(CT) imaging. In order to improve the clinical imaging sensitivity as well as to reduce the usage of contrast agents, we should enhance the imaging efficiency of contrast agents, and improve the phagocytic uptake by tumor cells. Therefore, it is worth to build a new platform which can not only enhance imaging efficiency, but also improve tumor cell phagocytosis of the contrast agents.Nanogels(NGs) are hydrophilic or amphiphilic polymer based polymeric compounds with an unique three dimensional network structure. NGs have numerous excellent characteristics, such as good stability, biocompatibility, high loading capacity, controllable size, simple synthesis, etc. Compared to conventional polymeric carrier, NGs having better flexibility and mobility can be easily uptaken by tumor cells. In addition, the NPs encapsulated into the internal gel structure can cause the synergy effect to improve the imaging efficiency. Poly-glutamic acid(γ-PGA) as a natural biodegradable polymer, has been widely used in drug delivery, wound dressings and tissue engineering. It is an ideal material to prepare NGs.In previous work, we adopted a moderate reduction and a sodium borohydride(NaBH4) reduction methods to synthesize polyethyleneimine(PEI)-coated Fe3O4 NPs and PEI-coated Au NPs, respectively. The PEI stabilized NPs displayed good water dispersion, colloidal stability, blood compatibility and cell compatibility. More importantly, they were able to be used as efficient nanoprobes for MR and CT imaging. The amine groups on the PEI surface can not only afford Fe3O4 or Au NPs with good colloidal stability, but also serve as a functional site for further modification to improve the biocompatibility and targeting specificity.In chapter 2, we developed Fe3O4 NP-loaded γ-PGA NGs using a double emulsion method. The formed NGs with a size of 152.3 ± 13.12 nm are water-dispersible and colloidally stable. The MR test shows the NGs have a relatively high r2 relaxivity. The results of in vitro cell viability and cellular uptake display that the NGs are quite cytocompatible in a given Fe concentration range, and can be uptaken by cancer cells at a superior level. The NGs are able to be used as a promising contrast agent for MR imaging of the xenografted tumor model in vivo. In addition, animal biodistribution data indicate that the NGs can be completely metabolized and excreted from the body without tissue toxicity. The developed hybrid NGs may hold great promise to be used as a novel contrast agent for MR imaging.In chapter 3, we synthesized Au NP-loaded γ-PGA NGs with a size of 108.6 ± 19.14 nm. The formed NGs are water soluble and colloidal stable. Compared to the clinical used CT contrast agents such as iohexol, the NGs display a higher X-ray attenuation intensity. The results of in vitro cell viability and cellular uptake display that the NGs are quite cytocompatible in a given Au concentration range, and can be uptaken by cancer cells at a superior level. The developed NGs are able to be used as a promising contrast agent for CT imaging of the xenografted tumor model in vivo. In addition, animal tissue distribution data indicate that the NGs can be completely metabolized and excreted from the body without tissue toxicity. The developed hybrid NGs may hold great promise to be used as a novel contrast agent for CT imaging.In summary, we developed a double emulsion approach to forming Fe3O4 or Au NP-loaded γ-PGA nanogels for MR or CT imaging. With the unique structure and versatile conjugation characteristics, the γ-PGA NGs may provide a unique nanoplatform for MR/CT imaging of different biological systems. |
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