Synthesis And Properties Of Near-Infrared Fluorescent Silica Nanoparticles

With the great development of biotechnology and medicine, fluorescent labeling technology is widely investigated and used in the field of disease diagnosis, detection of organic molecules and pharmacokinetic study. Among the great number of fluorescent dyes, cyanine dyes are one of widely-used fluorophores because of their easy adjustment in structure and optical properties, big molar extinction coefficient. Recently, one new kind of heptamethine cyanine dyes with large stokes shift, which were firstly found in our lab, have attracted researcher’s extensive attention. However, such cyanine dyes still have many shortcomings and deficiencies similar to traditional organic dyes, such as poor photo-stability, obvious solvation effect and so on. Nano-material dopping technology has greatly developed after it came out. The combination of organic dyes with inorganic nanomaterials takes advantages in showing potential to solve the above mentioned shortcomings. Noteworthly, fluorescent silica nanoparticles gains extensive attention of many researchers, because their simple preparation methods, easy surface functionalization, good biocompatibility, and no interference on spectra of organic dyes.In this work, we designed and synthesized two near-infrared heptamethine cyanine dyes with big stokes shift. Three different dopping methods were tried to dop the dyes inside silica nanoparticles by chemical bonding interaction. By optimizing the dopping methods of the dyes, we expect to gain fluorescent nanoparticles with smaller particle size, good dispersivity. For the Stober method, the size of the obtained fluorescent silica nanoparticles NIR-DDSNs-1was found too big (diameter>400nm) besides of aggregation and poor solubility in water, which limit NIR-DDSNs-1to be used in bioimaging application. For method two, a small silica nanoparticles-core (diameter-15nm) was employed to dop dyes to get the fluorescent silica nanoparticles NIR-DDSNs-2. Because of poor dispersity of the silica nanoparticles-core, the NIR-DDSNs-2also showed seriously aggregation, which makes NIR-DDSNs-2not an ideal fluorescent silica nanoparticles for bioimaging application too. Lastly, we used the method of inverse-phase microemulsion (W/O), by controlling the mass proportion of water and surfactant TX-100and the concentration of TX-100, optimizing the preparation conditions. Fortunately, we successfully prepared the fluorescent silica nanoparticles NIR-DDSNs-3with good dispersivity and the size about50nm in the end. Fluorescent silica nanoparticles NIR-DDSNs-3still have big stokes shift to avoid fluorescence self-quenching due to the intermolecular energy transfer in the nanoparticles. Less solvation effect of NIR-DDSNs-3was found compared their parent organic dye, which makes its signal more reliabile in fluorescence test. Based on well dispersivity, uniform particle size of50nm and near-infrared photo spectra of NIR-DDSNs-3, the fluorescence nanoparticles was used in fluorescence imaging in vivo through the method of tail vein inject on mice. It was found long-time fluorescence imaging (24h) in vivo can be achieved, and the fluorescent nanoparticles can be eliminated out by excretion from normal metabolism. We believe our prepared NIR-DDSNs-3has great potential in near-infrared fluorescence imaging.