(575a) Invited Speaker: Lipophilically-Functionalized Porous Silica Nanoparticles for Acoustic Imaging and Site-Specific Therapy

Ultrasound is widely applied in medical diagnosis and therapy due to its safety, high penetration depth, and low cost. In order to improve the contrast of sonographs and efficiency of ultrasound therapy, echogenic gas bodies or droplets (with diameters from 200 nm to 10 µm) are often used. However, because their inherent Laplace pressure limits both size and stability these fluid-filled colloids, they are not stable in circulation and have difficulty penetrating effectively into target tissues. Here we will present our work designing silica nanoparticles of ~100 nm with specifically-tailored surfaces that can nucleate the formation of ultrasound-responsive microbubbles under reduced acoustic pressures. This talk will discuss three aspects of this work. First, a comprehensive study was undertaken to determine the effect of structure on bubble nucleation and cavitation. A series of mesoporous silica nanoparticles were synthesized with sizes around 100 nm, each containing different morphologies. From these studies, the effects of nanoparticle porosity, surface roughness, hydrophobicity, and hydrophilic surface modification on acoustic cavitation inception by porous nanoparticles were determined. Second, particles with a hexagonal, small pore morphology were utilized for imaging in complex media while resisting protein fouling. Because the combination of surface roughness and hydrophobicity was necessary for nucleating bubble cavitation, proteins such as albumin adhering to the surface of the nanoparticle would be expected to quench signal entirely. The nanoparticles were found to provide effective image contrast even in whole blood and long-term storage. Finally, the therapeutic efficacy of the particles was determined by utilizing a phospholipid monolayer that was functionalized with PEG-lipid. The nanoparticles were uptaken into cancer cells by receptor-mediated endocytosis, and the cells with uptaken particles were killed selectively under HIFU insonation, as compared to cells without nanoparticles. Thus, these studies show how small nanoparticles can sensitize both bubble formation and cell death, thus overcoming the inherent Laplace limit found with fluid-filled particles.