Au- And Fe₃O₄-based Multifunctional Nanoprobes For Biomedical Imaging Application

With the development of nanotechnology, the functional nanoparticles have attracted a lot of attention. Among the various nanomaterials, gold and iron oxide nanoparticles have been paid much attention because of their unique optical and magnetic properties as well as the good biocompatibility and clinically practice. Gold nanoparticles and iron oxide nanoparticles have been applied in various biomedical applications to date, such as drug delivery, immunoassay, biomolecule separation, medical imaging and multimodality therapy, etc. In this thesis, we developed a series of gold and iron oxide nanoparticles based nanoprobes. Investigations on controllable synthesis, material properties tailoring, surface modification and biomedical application have been carried out. The main content of this paper includes the following aspects,?1? Tetrapod gold nanocrystals have been successfully prepared by a green and facile synthesis strategy. The properties of localized surface plasmon resonance ?LSPR? of these tetrapod gold nanocrystals have been tuned by a second growth approach. Factors influencing the properties like size, tips morphology and LSPR were investigated. The LSPR properties and extinction cross section of tetrapod gold nanocrystals were simulated by a finite-difference time-domain method. The results show that the tips of nanoparticles become longer and sharper with the LSPR peak shifting to longer wavelengths. The preparation of a series of tetrapod gold nanocrystals with tunable LSPR in the Vis-NIR region laid the ground work in further research of biomedical application.?2? Based on the prior study for tetrapod gold nanocrystals, the surface-enhanced Raman spectroscopy ?SERS? nanoprobes have been designed and successfully preparation. The construction of SERS nanoprobes were also optimized by selecting different branched gold nanoparticles and adjusting the addition of Raman reporters. The local electromagnetic field distribution of the various morphologies and tetrapod gold nanoparticles were simulated by a finite-difference time-domain ?FDTD? method. In vitro SERS imaging of stained breast cancer cells has also been demonstrated. These SERS nanoprobes have exhibited a good capability not only for Raman signal enhancement but also when successfully utilized as NIR SERS bioimaging nanoprobes. These SERS nanoprobes have great potential to apply in the field of biomedicine.?3? Fe₃O₄ nanoparticles synthesized via thermal decomposition have poor water dispersibility which strongly limits their development in biomedical application. Herein, we present a large-scale, facile and highly efficient strategy for phase transfer of oleic acid coated Fe₃O₄ nanoparticles via a strategy involved reverse micelles-based oxidative reaction. The strategy is able to shorten the reaction time, increase the yield of the nanoparticles with good water-dispersibility, high stability and good magnetic properties. In addition, the transferred Fe₃O₄ nanoparticles are used as T₂ contrast agent to perform magnetic resonance imaging of CNE2 cells ?nasopharyngeal carcinoma cell line? and in vivo imaging. Moreover, the strategy can not only obtain as-transferred Fe₃O₄ nanoparticles with terminal carboxyl groups which used for further functionalization, but also be expanded to other types of nanoparticles, having promising future in biomedical applications.?4? Au-Fe₃O₄ nanocomposites have been prepared by using condensation reaction of surface molecules of both nanoparticles. Gold nanoparticles were prepared by modified Frens' method and then coated by HS-PEG-NH₂. The as-transferred Fe₃O₄ nanoparticles which have terminal carboxyl groups were form strong linkage with the gold nanoparticles which have surficial amino groups. The as-prepared Au-Fe₃O₄ nanocomposites have great colloid stability, good biocompatibility and also combine the properties of optics and magnetics. In vivo MRI/CT imaging of Au-Fe₃O₄ nanocomposites has also been demonstrated. The nanocomposites have not only a good capability for MRI/CT imaging, but also great potential as nanoprobes for a wide range of field in bioimaging and therapy application.