Biocompatiable hollow silica microspheres as novel ultrasound contrast agents for in vivo imaging

Surface PEGylated hollow silica microspheres (PEG-HSS) of similar to 1250 nm in diameter were prepared by coating a thin layer of amino functionalized silica on the template of positive charged polystyrene, removing the template in THF solution, and further coupling the HSS with methoxy polyethylene glycol propionic acid (mPEG-COOH). Cytotoxicity tests, hemolysis assays, and confocal fluorescent imaging proved that the PEG-HSS have low cytotoxicity, good blood compatibility and cell permeability. Further in vitro ultrasound imaging of the as-prepared PEG-HSS in both physiological saline solution and human blood was investigated under different imaging conditions, including different ultrasound frequencies, mechanical indexes (MIs), and different PEG-HSS concentrations, which demonstrated obvious signal enhancement. In vivo ultrasound imaging was conducted on male rats after intra-testicle injection of the PEG-HSS. These results indicate that the PEG-HSS have great potential in application as a novel ultrasound contrast agent.