AVS 61st International Symposium & Exhibition
    Biomaterial Interfaces Monday Sessions
       Session BI+AS+NS-MoA

Paper BI+AS+NS-MoA2
Mechanically Optimized Fe (III) Doped Silica Nanoshells as a Contrast Agent for Ultrasound Imaging and HIFU Therapy

Monday, November 10, 2014, 2:20 pm, Room 317

Session: Bio/Nano Interfaces
Presenter: James Wang, University of California at San Diego
Authors: J. Wang, University of California at San Diego
A. Liberman, University of California at San Diego
R. Viveros, University of California at San Diego
C. Barback, University of California at San Diego
S.L. Blair, University of California at San Diego
Z. Wu, University of California at San Diego
R. Mattrey, University of California at San Diego
W. Trogler, University of California at San Diego
A.C. Kummel, University of California at San Diego
Correspondent: Click to Email

Ultrasound (US) is a common medical imaging modality due to its flexibility, low-cost and therapeutic potential. 500 nm silica nanoshells were synthesized as a contrast agent to improve US imaging signal for better diagnostic performance. Iron (III) was included into the silica network to enhance the biodegradability of the silica nanoshells. Previously, ferric iron was shown to facilitate silica nanoshell biodegradation due to its strong binding affinity with serum transferrin proteins. The removal of iron from the silica network by serum proteins fragments the nanoshells enabling effective biodegradation for in vivo applications. The silica nanoshells are filled with perfluorocarbon (PFC) vapor which expands and shatters the nanoshells during US irradiation. A mechanically weaker silica nanoshell increases US signal at lower power. A range of alkoxysilanes with selected R-groups such as long chain hydrocarbons, fluorinated carbon chains, fluorinated phenyl groups and vinyl groups were employed along with tetramethyl orthosilicate and iron (III) ethoxide in a modified sol-gel synthesis to create structural defects that alter the mechanical properties of the nanoshells. Monodispersed 500 nm polystyrene beads were used as a soft template during the reaction. The silica nanoparticles were calcined at 550 C to remove the polystyrene core and form hollow nanoshells. SEM and TEM showed that 500 nm silica nanoshells with different microstructures were synthesized incorporating alkoxysilanes with different R-groups. Formulations with higher concentrations of alkoxysilanes with large R-groups such as long chain hydrocarbons resulted in stronger in vitro contrast enhanced ultrasound (CEUS) signals due to the increase of structural voids that resulted in weaker shell strength. CEUS experiments demonstrated that mechanically weaker silica nanoshells exhibited longer signal life time and required a lower mechanical index (MI) for imaging. The high intensity focused ultrasound (HIFU) properties of the modified silica nanoshells were tested for potential therapeutic applications. Mechanically weaker silica nanoshells were shown in vitro to require a lower HIFU power to fracture which is consistent with safer HIFU therapy. By synthesizing strength tunable silica nanoshells as US contrast agents, it is possible to improve diagnostic US imaging performance in order to detect smaller tissue structures or early stage tumors. Additionally, mechanically weaker silica nanoshells may also increase the efficiency of HIFU enabling HIFU at lower US power and/or higher speed.