UC San Diego

Silica has become a high interest material for biomedical applications due to low toxicity, facile and robust synthetic methods, and precise control over particle size, shape and surface properties. Silica and iron-silica nanoshells have been developed which are synthesized via sol-gel method on polystyrene templates and calcined to yield hollow rigid nanoshells which were subsequently filled with vaporized perfluoropentane (PFP) or liquid PFP. Incorporating iron into the shells renders the particles biodegradable through iron chelation proteins and the PFP provides the increased ultrasound scattering. The sum of these properties make silica nanoshells an excellent potential candidate for ultrasound mediated applications. There are over 200,000 cases of breast cancer in the US alone each year and surgery is currently the primary course of treatment. Unfortunately, in many of these cases the tumor is not readily observable during surgery resulting in the need for preoperative localizations. Guide-wire localization results in between 20-50% of patients requiring second surgery due to incomplete resection and seed localization is rarely performed. Perfluoropentane loaded nanoshells have been applied as a color Doppler ultrasound contrast imaging agent which can act as small volume (100 ul) injectable stationary guide-marker for breast tumor resection. Experiments have demonstrated that the nanoshells can provide robust contrast for periods exceeding a week in vivo positioning them as a potential future stationary surgical marker. Additionally, it has been shown in preliminary experiments that a secondary application exists for nanoshells in high intensity focused ultrasound (HIFU) therapy which is already in clinical use for the ablation of uterine fibroids and is in clinical trials for various cancer therapies. The nanoshells act as a sensitizing agent for thermal ablation and histotripsy therapy increasing scattering of the ultrasound and reducing the cavitation threshold which can result in faster lower power therapy