A strategy for fabrication of uniform double-shell hollow microspheres as effective acoustic echo imaging contrast agents through a new polymer-backbone-transition method

We present a novel self-templating strategy for directly fabricating monodisperse hollow polymer microspheres (HPMs) from vinyl-containing organosilica microspheres (VOMs) through a polymer-backbone-transition method (PBTM). The VOMs play the roles of both templates and precursors in the new shells. The uniform HPMs with varying sizes from 320 nm to 1.6 mu m could be obtained by controlling the diameter of the VOMs. Depending on the progress of outer-to-inner shell formation, the range of shell thickness is broadly tunable from 15 nm to 290 nm. Theoretically, through introduction of a suitable vinyl monomer in the shell-formation step, a variety of double-shell hollow polymer microspheres (ds-HPMs) could be fabricated based on this strategy. We then synthesize ds-HPMs by copolymerization of VOMs with N-isopropyl acrylamide (NIPAM) in order to improve the dispersion stability of HPMs in water and provide better oscillation and compressibility. In vitro and in vivo experimental results showed that the ds-HPMs possessed excellent echoing characteristics which could be applied as ultrasound contrast agents for the real-time guidance during the surgical process.