Abstract
Engineered Nanomaterials (ENM) have rapidly emerged as vital components in modern technology, most notably as vehicles in vaccine delivery, which highlights their growing potential for interaction with biological and environmental systems. One critical property influencing ENM behavior is dissolution, the release of ions and molecules into surrounding media, which dictates their abundance, fate, and biological response. A decade ago, dissolution was recognised as pivotal in understanding ENM interactions with exposure media and assessing their potential toxicity. Since then, progress in this field has led to a deeper understanding of ENM surface chemistry and transformations, positioning dissolution as a key factor in achieving "Safety-by-Design" (SbD) for sustainable ENM applications. Early dissolution studies relied on batch and flow-through methods, such as dialysis, but recent advances have favored in situ techniques such as single-cell/single-particle inductively coupled plasma mass spectrometry (ICP-MS) and liquid-cell electron microscopy, enabling real-time dissolution measurements. Additionally, computational models can now predict ENM reactivity and stability, enhancing the understanding of dissolution behavior. This perspective critically examines these developments, highlighting computational approaches for their efficiency and scalability, and proposes a roadmap to integrate these insights with SbD goals for safer, sustainable nanotechnology applications.