Gold Nanocones: A Candidate for Cavitation-Enhanced Drug Delivery

Title: Gold Nanocones: A Candidate for Cavitation-Enhanced Drug Delivery

Authors: Xiaoqian Su and James J. Kwan

Ultrasound is a high frequency longitudinal pressure wave. With sufficient energy, ultrasound is capable of nucleating cavitation: the dynamic oscillations of a gas or vapour cavity. Cavitation promotes a multitude of mechanical effects, including, jetting, shockwaves, and microstreaming. These mechanical effects have been established to be key mechanisms in ultrasound-enhanced the delivery of therapeutics for a broad range of clinical applications such as cancer therapy. However, the nucleation of cavitation with ultrasound alone requires energies that are damaging to surrounding tissue. Therefore to remove off target damage, particles that generate cavitation, i.e., cavitation agents, are required.

Conventional cavitation agents, i.e., ultrasound contrast agents, have demonstrated the ability to enhance drug delivery. Yet the potential for enhanced therapy from these particles in certain therapies are limited because of their large size and rapid acoustic destruction short lifetime. We have previously demonstrated that the use of a single cavity polymeric nanoparticles that trap nanobubbles, provide sustained cavitation, and improved cancer drug delivery¹. However, the acoustic energy requirements to nucleate sufficient cavitation was substantial. Here, we show an effective method to manufacture gold nanocone cavitation agents. Furthermore, the unique structure of the gold nanocones enables the formation of clustered bellflower super structures with multiple cavities, which will reduce the acoustic energy requirements for cavitation. To measure the acoustic responses of these novel cavitation agents, we expose these particles to increasing pressure amplitudes until cavitation is observed with a passive cavitation detector. The result here will aid in the design and manufacture of the next generation ultrasound-responsive nanoparticles for ultrasound-enhanced drug delivery.

1     Kwan, J. J. et al. Ultrasound©\Propelled Nanocups for Drug Delivery. small 11, 5305-5314 (2015)

Keywords: ultrasound, drug delivery, cavitation, nanoparticles