Sonosensitive Nanoparticles for Controlled Instigation of Cavitation and Drug Delivery by Ultrasound

Reliable instigation of cavitation in-vivo during ultrasound therapy is notoriously difficult. Lowering the peak rarefractional pressure required to initiate cavitation (the cavitation threshold) has been previously addressed using ultrasound contrast agents in the form of encapsulated stabilized micron scale bubbles. These agents lack stability and are generally too large to extravasate into tumours and other target tissues. Solid nanoparticles are proposed as novel cavitation nucleation agents, which overcome these limitations. Such agents are manufactured to achieve high surface roughness and hydrophobicity, facilitating air entrapment upon drying, thus harboring an abundance of cavitation nucleation sites. These nanoparticulate nucleating agents have been found to lower the cavitation threshold significantly in aqueous biological media, enabling reproducible cavitation activity during repeated exposure to therapeutic ultrasound. This paper investigates the engineering of core-shell nanoparticles and examines their ability to initiate inertial cavitation in the context of ultrasound-enhanced localized drug delivery for cancer. Core-shell nanoparticles have been found to decrease the peak focal pressure where the probability of cavitation is greater than 0.5, by factors of five-to ten-fold, dependent on particle size, total surface area and surface morphology.