| AVS 61st International Symposium & Exhibition | |
| Biomaterial Interfaces | Wednesday Sessions |
| Session BI+MG-WeA |
| Session: | Design and Discovery: Biointerfaces |
| Presenter: | Alexander Liberman, University of California at San Diego |
| Authors: | A. Liberman, University of California at San Diego C. Barback, University of California at San Diego R. Viveros, University of California at San Diego S.L. Blair, University of California at San Diego D. Vera, University of California at San Diego L. Ellies, 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 |
As a safe alternative to intrasurgical guidewires and implantable radioactive seeds, gas-filled hollow Fe-doped silica particles have been developed, which can be used for ultrasound-guided surgery for multiple foci. The function of the Fe doping is to render the silica shells biodegradable. The particles are synthesized through a sol-gel method on a polystyrene template, and calcined to create hollow, rigid nanoshells. The Fe-doped silica shell is derived from tetramethyl orthosilicate (TMOS) and iron ethoxide, which forms a rigid, nanoporous shell upon calcination. The nanoshells are filled with perfluoropentane (PFP) vapor or liquid. The flourous phase is contained within the porous shell due to its extremely low solubility in water. In vitro studies have shown that continuous particle imaging time is up to approximately three hours non-stop. In vivo particle injection longevity studies have been performed in tumor bearing mouse models show signal presence with color Doppler imaging up to ten days post injection. To study biodistribution, nanoshells were functionalized with DTPA and radiolabeled with Indium-111 and then imaged by gamma scintigraphy over 72 hours. Scintigraphic imaging and gamma counting confirm that particles undergoing IV delivery to tumor bearing mice will passively accumulate in the tumors which may allow for tumor detection and therapuetic applications. Additionally, long term biodistribution studies in mice have shown a steady decrease in silicon content over the course of 10 weeks by inductively coupled plasma optical emmision spectroscopy (ICP-OES).
These silica shells break under acoustic excitation to release uncovered gas pockets which increase acoustic energy absorption and reduce acoustic cavitation threshold locally. Therefore they may also be employed as a sensitizing agent in high intensity focused ultrasound (HIFU) therapy. Traditional ultrasound agents which can be used as a HIFU senstizing agent pose several potential drawbacks such as poor in vivo persistence (minutes) and high risk during continuous perfusion. Preliminary in vivo HIFU ablation studies show that very few particles are needed in order to develop a sensitizing effect to HIFU thereby substantially reduce the amount of HIFU exposure necessary to achieve an ablative effect. It was found that nanoshells systemically adminstered to breast tumor bearing mice could be cavitated by HIFU 24 hours after administration. This mechanical cavitation caused liquification within the focal volume of the HIFU which contained the nanoshells within seconds of the HIFU application. This may potentially allow for a larger area to be ablated in less time with less power.