Synthesis And Biomedical Application Of Multifunctional Nanoparticles Based On Hollow Gold Nanospheres

Theranostic agents with both imaging and therapeutic functions in one single entity can realize the early diagnosis and treatment of tumor, providing a scientific guarantee of early diagnosis and early treatment for cancer. Among numerous diagnostic reagents, multifunctional magnetic- gold nanocomposites have attracted numerous attentions for the combination of excellent magnetic properties from magnetic nanomaterials and good optical performance from gold nanomaterials. Much effort has been made for multifunctional magnetic-gold nanocomposites. However, most of these magnetic- gold nanocomposites focused on gold nanorods or nanoshells, few studies have been reported for the hollow gold nanospheres(HGNs)- magnetic hybrid nanoparticles and the applications of them for the multimodal imaging and(photothermal therapy) PTT have not yet been reported. Compared with other gold nanostructures, HGNs have the unique advantages of small size(~50 nm), spherical shape, strong and tunable absorption at NIR and especially a hollow interior which can be loaded other functional agents, such as antitumor drugs, to realize combined PTT and chemotherapy. We developed a novel probe based on magnetic-gold nanocomposites with HGNs as cores and Fe3O4 NPs as satellites. Folic acid(FA) as a target molecule was conjugated on it. This kind of nanostructures can realize the MRI/PAI and PTT functions at the same time. In addition, combined the high sensitivity advantage of fluorescence imaging, we developed a multifunctional nanocomposite that can be applied to PAI and fluorescence imaging. After loading the antitumor drug doxorubicin(DOX), it can realize PTT and chemotherapy at the same time. The specific research contents include:(1) The synthesis and characterization of multifunctional magnetic hollow gold nanospheres HGNs@Fe3O4-FA. Firstly, water-soluble HGNs were synthesized via galvanic replacement of cobalt NPs. Then superparamagnetic iron oxide nanoparticles(Fe3O4 NPs) were synthesized by polyol process and mercapto modification was achieved via ligand exchange process.They can couple with HGNs through Au-S bond. At last, FA was coupled on the surface of HGNs using cysteamine hydrochloride as a linker and DCC/NHS as coupling reagent. The characterization of the HGNs@Fe3O4-FA nanoparticles confirmed that the nanoparticles exhibted good MRI/PAI dual- mode imaging abilities and good thermal conversion effect.(2) The synthesis and characterization of multifunctional fluorescent drug- loading nanoparticles HGNs@RhB@BSA-DOX. First of all, fluorescent dye rhodamine B(RhB) was coupled with bovine serum albumin(BSA) through coupling agent EDC/Sulfo-NHS. Then, BSA was modified on HGNs through Au-S bond. Finally, antitumor drug doxorubicin(DOX) was loaded onto the nanoparticles by the electrostatic and hydrophobic interaction. The nanoparticles were characterized with ultraviolet spectrograph, fluorescence spectrometer and ZetaSizer analyzer.(3) Cytotoxicity of the HGNs@Fe3O4-FA nanoparticles were assessed with MTT assay and the nanoparticles were applied to in vitro MRI/PAI and PTT. The MTT assay showed that even when the concentration of nanoparticles were as high as 200 ?g/mL, the cells still have the survival rate of above 80%, indicating the low toxicity of nanoparticles. In vitro targeted bimodal imaging(MRI and PAI) and PTT of cancer cells were carried out. The results demonstrated that they can act as both imaging agents for MRI/PAI and therapeutic agents for PTT and would have great potential in cancer theranostics.