This project provides the first systematic, molecular-scale framework linking nanoparticle–matrix interactions and ultrasound (US) parameters to transport enhancement in polymeric networks. Our findings identify NP retention strength and US exposure characteristics as the primary determinants of acoustically enhanced diffusion, offering a mechanistic explanation that reconciles previously contradictory experimental observations. This framework can guide the rational design of ultrasound-mediated drug delivery protocols in biological hydrogels and tumour extracellular matrix (ECM).
While our coarse-grained Langevin Dynamics approach enables controlled, bottom-up investigation, it necessarily simplifies the ECM as a homogeneous, periodic polymer network. Future work should incorporate structural heterogeneity, variable crosslinking, and patchy interactions to better capture in vivo conditions. Similarly, hydrodynamic effects are currently represented through friction terms, omitting long-range coupling between NPs, the network, and surrounding fluid; explicit modelling of these interactions will be important for predictive accuracy.
Thermal effects of US, excluded here via constant-temperature control, may influence in vitro systems but are expected to be physiologically regulated in vivo.
Addressing these aspects through extended modelling and targeted experiments will be essential for translating these insights into clinical strategies, supporting further research, experimental validation, and eventual integration into personalised nanomedicine delivery systems.
