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

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.