Research On Nano-sensing And Nano-delivery Techniques And Their Applications In Biomedicine

The development of bionanotechnology has provided many new opportunities for the research of biology and medicine. However, many efforts are needed to further develop their applications. Recently, our group has developed a biocompatible core-shell nanoparticle and has carried out systemic researches with the combination of nanotechnology, analytical chemistry, biotechnology and material science. On the basis of our correlative researches, this dissertation focuses on the studies of the nanosensors and gene carriers based on nanoparticles and their applications in the biomedicine.1. We synthesized a nanoparticle and utilized it as a pH nanosensor for noninvasive monitoring intracellular pH change induced by drug stimulation. The pH sensor was a two dye doped silica nanoparticle (2DFNS) that contained a pH sensitive indicator (FITC) and a reference dye (RuBPY). The 2DFNS had an average diameter of 42±3nm and could be well dispersed in aqueous solution. This allowed it to be easily taken up by cells for noninvasive intracellular pH measurement. The 2DFNS had excellent pH sensing capability and reproducibility. The dynamic range of the nanosensor was between pH 4 and 7 with a sensitivity of 0.05 pH units. The 2DFNS could act as sensitive ratometric nanosensors for monitoring pH change and the calculation of pH was independent on cell number and dye concentration. This new 2DFNS was used for intracellular pH measurement in a variety of biological samples. Lysosomal pH change in murine macrophages stimulated by chloroquine and intracellular acidification in apoptotic cancer cells were monitored. The 2DFNS was stable and reproducible. There was no dye leakage and the photosatbility was excellent. The biological applications of nanosensors have demonstrated their excellent utility in intracellular measurements. It is possible to develop multiple-analyte sensors by the encapsulation of multiple sensitive dyes, given their high sensitivity and extremely simple fabrication.2. Bio-functioned fluorescent silica nanoparticles have been synthesized for cell labeling and cell differentiation and have shown great promise as novel fluorescent probes. The galactose-conjugated fluorescent nanoparticles (GCFNPs) were synthesized by the conjugation of amino-modified fluorescent nanoparticles with lactobionic acid (LA) through EDC linkage. This yielded GCFNPs retained excellent biological activity and could be used to label the hepatocyte as an...