Langevin dynamics modeling for mechanistic insights into ultrasound triggered drug release from gold nanoparticle conjugates

Abstract

Harnessing the responsiveness of metal nanoparticle–drug conjugates to external stimuli enables tunable therapeutic release with spatial and temporal accuracy. However, elucidating and modeling the underlying release mechanisms over experimentally relevant timescales remains a challenge. In this work, we present a minimal statistical model based on Langevin dynamics to study the long-timescale dynamics of drug release from citrate-capped gold nanoparticles (CIT–AuNPs) under ultrasound (US) exposure. In addition to interaction between participants due to Lennard-Jones and Coulomb potentials, the model incorporates various US-induced effects, revealing that acoustic streaming and cavitation are the driving forces for drug release. Complementary UV–visible and surface-enhanced Raman spectroscopy measurements confirm the release dynamics in the CIT–AuNP–drug conjugate during US exposure, while fluorescence spectroscopy quantifies the release efficiency. Together, these results highlight the efficacy of a minimal multiscale modeling approach in unraveling the physical mechanisms underlying US-mediated drug release and guiding the design of responsive nanocarrier systems.