Ultrasound (US)  in combination with nano/microbubbles  is a promising method to improve the delivery of drugs and genes into living cells [1]. The basic idea is that under US exposure, bubbles may stably compress and expand, a regime called stable cavitation, which generates liquid flows around the bubbles. Bubbles may also oscillate non-linearly and expand until collapse, called the inertial cavitation regime, generating jetting and shock waves. These hydrodynamic effects cause different biophysical and biochemical cell responses, which could facilitate the delivery of drugs and genes into cells [2].

The noninvasive nature, low toxicity, local application, cost effectiveness and potential to achieve imaging-guided therapy are significant advantages of the US mediated drug delivery method. Therefore, in the last two decades, both experimental and theoretical studies have been intensively performed to get in-depth understanding on how the ultrasound-induced drug uptake is influenced by the properties of bubbles and cells, by acoustical driving parameters and bubble/cell micro-environment. Despite advances in the field, there are still large discrepancies among in-vitro, in-vivo and modelling studies. Moreover, there are variations in drug delivery outcomes, and the delivery efficiency is still rather low [2]. However, the method has been tried in a brute manner to treat various diseases such as Alzheimer’s disease, cardiovascular disease, infections and cancer [3]. However, why this emerging drug delivery paradigm has not yet reached widespread clinical use? The entire process from bubble cavitation up to animal and human clinical therapeutic effects spans over very large spatiotemporal scales, from picoseconds to days, thus a deep understanding of the bubble-cell interaction mechanism is challenge.

Currently, microscopy-based techniques are ideal for capturing the spatiotemporal dynamics of bubble dynamics and cell response in the microsecond and micrometer scales. However, experimental approaches are difficult to access simultaneously to the bubble dynamics and cell response in the earlier stages, which especially happen in the picosecond-microsecond range, and nanometer length scale. In principle, MD simulation has the potential to reveal the mechanisms of bubble cavitation and cell response at the atomistic/molecular levels and short timescales [4-9]. However, there is a scarcity of MD simulation studies specifically focused on bubble cavitation and cell response. This could be attributed to the limitations of MD simulation when it comes to large spatiotemporal scales. The particle based simulation and mathematical modelling can address intriguing problems of bubble behaviour and cell response across both short and large spatiotemporal scales [10-15]. However, these approaches often lack molecular-level details in their analyses. As a result, there is a gap between MD simulation and experimental observations. One of our objectives through this workshop is to explore how MD simulation can complement theoretical modelling and experiment, thereby enhancing its role in the field of bubble cavitation for improved drug delivery. Additionally, we will explore topics such as nanobubble cavitation-controlled regimes for effective molecular internalization, optimization of ultrasound and bubble parameters, and the molecular mechanisms underlying drug uptake.