Study On The Bioeffects Of Different Functional Groups-Modified Silica Nanoparticles In Vivo

With the fast development of bionanotechnology, the application of bionanomaterials in the biomedicine has been to a new phase. Meanwhile, the bioeffects of the bionanomaterials have gradually become a common concerned problem in the research fields flowing the research and exploitation of bionanomaterials and bionanosensors. Silica nanoparticles, as one of the important nanomaterials, display several features of straightforward synthesis and easily modification, which make them be widely applied in biomedicine. However, The bioeffects of silica nanoparticles in vivo have not been systemically studied. Aiming at the direction of the bioeffects of silica nanoparticles in vivo, different functionalized groups-modified silica nanoparticles with good dispersion have been prepared firstly, and then the bioeffecteds of the different functionalized groups-modified silica nanoparticles in vivo have been investigated. The three parts of the thesis are as follows.1. Study on the different functionalized groups-modified silica nanoparticles preparation and dispersibility.Silica nanoparticles (SiNP), amino-teminated silica nanoparticles (NSiNP), carboxyl-terminated silica nanoparticles (CSiNP) and PEG-terminated silica nanoparticles (PSiNP) were prepared via the synchronous modification of functional group in water-in-oil microemulsion (hereinafter referred to being modified in oil) and the modification of functional group on the well-prepared SiNP (hereinafter referred to being modified in water) respectively. The dispersibility of different functionalized silica nanoparticles in water suspension was evaluated with sediment velocity and centrifugation velocity. And further analysis of the dispersion behavior was demonstrated through the TEM imaging and hydrodynamic size analyses. The results indicated that the following order of dispersion was observed: CSiNP≧PSiNP﹥SiNP﹥NSiNP, when the silica nanoparticles were modified with the same method. In addition, for CSiNP and PSiNP, the dispersibility of the two nanoparticles modified in oil was superior to that of modified in water. At the same time, the nonspecific adsorption of the different functionalized silica nanoparticles modified in oil with the Hela cells was also investigated. There was almost no nonspecification with Hela cells to CSiNP and PSiNP. However, the NSiNP were adsorbed to the Hela cells extensively. 2. In vivo biodistribution of the different functionalized groups-modified silica nanoparticles by using an optical in vivo imaging system.The biodistribution of SiNP, CSiNP and PSiNP with size of ~45 nm prepared through the method of modification in oil has been montitored in vivo, in situ and real time by using an optical in vivo imaging system. The results demonstrated that the three types of SiNP were seen to distributed around the whole body after injection from the tail veins, respectively. Subsequently, as blood circulates, the SiNP and CSiNP were exhibited prominent distribution in the liver, urinary bladder and kidney. By comparison, the PSiNP still remained visible in circulation, and presented lower liver uptake than SiNP and CSiNP. The circulation lifetime obtained by in vivo imaging revealed that PSiNP exhibit a much longer blood circulation time (t1/2=180±40 min) than SiNPs (t1/2=80±30 min) and CSiNPs (t1/2=35±10 min). Furthermore, ex vivo optical imaging of some organs directly removed from the anatomized mice were first acquired during necropsy to confirm the in vivo optical imaging results. It was clear that the three different functionalized groups-modified silica nnoparticles inside biological organs obtained through ex vivo optical imaging of organs agreed with the in vivo optical imaging data.3. Study on renal excretion and preliminary excretion mechanism of silica nanoparticles.The phenomenon that the fluorescence emitted from the kidneys and bladders of the mice i.v. injected SiNP, CSiNP, PSiNP with size of ~ 45 nm has been obviously observed in chapter 3, which made us hypothesize that parts of iv. injected three different funtionalized groups-modified silica nanoparticles in vivo could be possibly all excreted from the renal route. In order to confirm the conjecture, in vivo excretion process imaging of, i.v. injected SiNP, CSiNP, PSiNP, imaging of the collected urine from the mice i.v. injected SiNP, CSiNP, PSiNP, TEM imaging and energy-dispersed X-ray spectrum analysis of the collected urine samples have been investigated. The results convinced that the three type i.v. injected SiNP, CSiNP, PSiNP with a size of ~ 45 nm can all be partly excreted into urine through the renal route. Furthermore, in order to study the primary excretion mechanism of silica nanoparticles, the excretion behavior of Rubpy dye molecules with that of Rubpy dye doped PSiNP has been compared after which were injected from the aortic arch of rats.