Study On The In Vivo Bioeffects Of Silica Nanoparitcles With Different Sizes

With the fast development of bionanotechnology, the application of nanomaterials in the biomedicine has been to a new phase. At the same time, the bioeffects of the nanomaterials have also gradually become a common focus following the research and exploitation of bionanomaterials and bionanosensor. As one of the kinds of nanomaterials, silica nanoparticles have been widely appllied in biomedicine for its straig htforward synthesis and easily modification. As a result, the potential bioeffect of silica nanoparticles researc his being now gained attention. However, the bioeffects of silica nanoparticles with different sizes in vivo have not been systemically studied. Aimed at this advanced research direction, a series of studies on bioeffects of silica nanoparticles and PEGlyated silica nanoparticles with different size in vivo have been carried out in this thesis. They are as follows:1. Study on the preparation of size-controlled silica nanoparticles based on reverse microemulsion methodThe preparation of size-controlled silica nanoparticles using base-catalyzed hydrolysis of tetraethyl orthosilicate (TEOS) in Triton X-100/cyclohexane/ hexanol/water reverse microemulsion system has been investigated. The effects of the water-to-surfactant molar ratio (R), amounts of ammonium hydroxide and TEOS, shell coating times on the size of silica nanoparticles have been investigated, respectively. The results showed that the size of the prepared silica nanoparticles could be well controlled by changing some parameter of the reaction system as followed. The water-to-surfactant molar ratio (R) was the main factor of the parameters on the size of the silica particles. The particles'size was decreased obviously with increase of R. And increased with amounts of ammonium hydroxide, the size of silica particles was first decreased and then was not changed. The size and dispersibility of the prepared silica nanoparticles also changed obviously with increase of the shell coating times. However, the amounts of TEOS almost had no effect on the particles'size. These results provided practical foundation for the preparation of size controlled silica nanoparticles.2. Study on the in vivo bioeffects of silica nanoparticles with different sizesAccording to the method of synthese of size-controlled silica nanoparticles as above, we prepared a series of RuBpy doped silica nanoparticles with different sizes of 118.4±6.0 nm, 72.1±5.3 nm, 46.7±4.2 nm and 26.1±5.4 nm, respectively. Then BLAB/C-nu mice were intravenously injected in the tail vein with the four kinds of fluorescent silica nanoparticles, respectively. The tissue distribution and pharmacokinetics of the i.v. injected fluorescent silica nanoparticles were investigated by in vivo imaging, organ imaging and tissue slice ex vivo, urine fluorescence imaging. The in vivo fluorescence imaging results showed that the 118.4±6.0 nm and 72.1±5.3 nm fluorescent silica nanoparticles accumlated in the liver once the nanoparticles injected the body via the tail vein. And the flurorescence signal of bladder of mice injected with 72.1±5.3 nm silica nanoparticles could be observed. The flurorescence signal of the whole body of mice injected with 46.7±4.2 nm and 26.1±5.4 nm fluorescent silica nanoparticles was obversed, but with the extension of time the nanoparticles could be removed from the peripheral blood, and the half-life time are 7.1 min and 25 min, respectively. Organ and tissue ex vivo fluorescence imaging results showed that the silica nanoparticles were retained in the liver, kidney and spleen mainly, and were taken up by the lung in varying degrees. The urine fluorescence imaging showed that the fluorescent silica nanoparticles of 118.4±6.0 nm could not be excreted from mice via the renal following intravenously adminstration. However, the other three sizes of fluorescent silica nanoparticles could be partly excreted from mice via the renal.3. Study on the in vivo bioeffects of PEGylated silica nanoparticles with different sizesBased on the study of in vivo bioeffects of silica nanoparticles with different sizes, the tissue distribution and pharmacokinetics of 123.1±6.0 nm, 68.5±4.9 nm, 47.0±6.1 nm, and 32.6±4.7 nm PEGlyted silica nanoparticles were further investigated. The in vivo fluorescence imaging results showed that flurorescence signal was obviously observed in the whole body and bladder in the mice injected with 123.1±6.0 nm PEGlyate silica nanoparticles. With extension of time, the PEGlyate silica nanoparticles gradually accumulated in the liver. To 68.5±4.9 nm, 47.0±6.1 nm and 32.6±4.7 nm PEGlyated silica nanoparticles, the strong flurorescence signal of the whole body in mice was obversed even after 4 hour post injection, and the blood circulation time had been prolonged greatly. Organ and tissue ex vivo fluorescence imaging results showed that the four PEGlyated silica nanoparticles were distributed in various organs. The fluorescent silica nanoparticles levels were higest in the kidney. And the PEGlyated silica nanoparticles were more easily accumulated in the liver with increace of size. The urine fluorescence imaging showed that the four kinds of PEGlyated fluorescent silica nanoparticles could both be partly excreted via the renal following intravenously adminstration. The results showed that PEGlyated fluorescent silica nanoparticles significantly extend the blood circulation time and reduced the uptake by the reticuloendthelia system (RES), such as liver.