Revisiting Colloid Theory for Biomedicine: Reconciling Simple Models in Complex Environments.

Colloidal science provides predictive frameworks for particle stability and interactions, yet applying these classical models to biological systems requires extending them to account for the complex and dynamic conditions present in physiological environments. Theories such as Derjaguin-Landau-Verwey-Overbeek (DLVO) were developed to describe interactions in carefully defined colloidal systems. When applied to biological environments, additional factors, including soft interfaces, evolving protein adsorption layers, and macromolecular crowding, must be incorporated to capture the full interaction landscape. Consequently, nanoparticles designed under traditional assumptions often behave unpredictably in vivo. This Perspective reframes colloidal science through a biological lens, emphasizing that particle behavior in physiological media is governed by protein corona formation and interactions with soft, charged, and crowded interfaces such as tumors and mucus. Integrating these disciplines requires integrating colloids and biomedical engineering, standardizing nanoparticle characterization techniques in biological media, and prioritizing interface-driven research to enable predictive, clinically relevant nanomaterial design.