Multiphysics Modeling of Low-Intensity Pulsed Ultrasound Induced Chemotherapeutic Drug Release from the Surface of Gold Nanoparticles

SIMPLE SUMMARY: In targeted chemotherapy, ultrasound can be used to induce the release of anticancer drugs from nanoparticle drug carriers. Our previous study found that after exposure to low-intensity pulsed ultrasound, doxorubicin was released from gold nanoparticle drug carriers, and aggregation of the gold nanoparticles was observed. Currently, no theoretical model of ultrasound-induced drug release from gold nanoparticles exists in the literature. However, DLVO theory can be used to predict the aggregation of colloidal particles. In this work, DLVO theory was applied to predict whether the release of doxorubicin from gold nanoparticle drug carriers would happen under low-intensity pulsed ultrasound exposure. Attractive van der Waals and repulsive electrostatic potentials were calculated for any gold nanoparticle pair, and the total interaction potential was found before and after ultrasound exposure. A threshold for gold nanoparticle aggregation, which indicates doxorubicin release, was then found. ABSTRACT: Currently, no numerical model for low-intensity pulsed ultrasound (LIPUS)-triggered anticancer drug release from gold nanoparticle (GNP) drug carriers exists in the literature. In this work, LIPUS-induced doxorubicin (DOX) release from GNPs was achieved in an ex vivo tissue model. Transmission electronic microscopy (TEM) imaging was performed before and after LIPUS exposure, and significant aggregation of the GNPs was observed upon DOX release. Subsequently, GNP surface potential was determined before and after LIPUS-induced DOX release, using a Zetasizer. A numerical model was then created to predict GNP aggregation, and the subsequent DOX release, via combining a thermal field simulation by solving the bioheat transfer equation (in COMSOL) and the Derjaguin, Landau, Verwey, and Overbeek (DLVO) total interaction potential (in MATLAB). The DLVO model was applied to the colloidal DOX-loaded GNPs by summing the attractive van der Waals and electrostatic repulsion interaction potentials for any given GNP pair. DLVO total interaction potential was found before and after LIPUS exposure, and an energy barrier for aggregation was determined. The DLVO interaction potential peak amplitude was found to drop from 1.36 k(B)T to 0.24 k(B)T after LIPUS exposure, translating to an 82.4% decrease in peak amplitude value. It was concluded that the interaction potential energy threshold for GNP aggregation (and, as a result, DOX release) was equal to 0.24 k(B)T.