Biomolecular Transformations Shape the Environmental Fate of Nanoscale and Emerging Materials

ConspectusEngineered nanomaterials (ENMs) have revolutionized biomedicine, energy, and environmental remediation due to their unique physicochemical properties. However, these properties are not static; they evolve dynamically as ENMs interact with real-world biological and environmental systems. Central to this transformation is the formation of the biomolecular corona, a dynamic layer of adsorbed proteins, lipids, and metabolites that govern how nanomaterials interface with their surroundings. The corona alters the surface chemistry, colloidal stability, and biological identity of an ENM, ultimately dictating its environmental fate, functionality, and safety profile, but also evolves as the surroundings change or as the living system responds to the presence of the nanomaterials and secreted biomolecules.Over the past decade, our research has elucidated how biomolecule-driven transformations, such as dissolution, ion release, sulfidation, enzymatic degradation, and redox reactions, can be modulated by the acquired corona. These processes not only determine the longevity and toxicity of nanomaterials but also offer programmable opportunities for safe degradation or detoxification. For instance, coronas can enhance or suppress ion leaching and catalyze phase changes into less bioavailable forms.We have also explored the role of eco-coronas, formed in environmental matrices like soil or aquatic systems, which contain a broader range of biomolecules beyond proteins, such as humic acids, polysaccharides, and microbial secretions. These coronas initiate transformation cascades as ENMs transition through different environmental compartments, influencing mobility, speciation, and bioavailability to organisms. Through this lens, we view ENMs not as inert entities but as evolving systems shaped by dynamic biological interactions.While the biomolecular corona concept is well-established for engineered nanomaterials such as metal and polymeric nanoparticles, it is now extending to emerging materials such as metal-organic frameworks (MOFs). These hybrid, porous materials are increasingly used in biomedical, catalytic, and environmental applications, yet their transformations under biological and ecological conditions remain largely uncharted. We argue that applying corona concepts to MOFs provides a powerful lens to anticipate their environmental fate and guide safe-and-sustainable design. Our recent work demonstrates that protein coronas can either stabilize or destabilize MOFs, modulate enzyme function, or even program degradation via enzyme-sensitive linkers. These findings provide the foundation for safe-by-design and corona-informed design strategies, where materials are engineered to respond predictably to biological cues.This Account integrates advances in <i>in situ</i> characterization, machine learning, and predictive modeling to chart a path toward programmable, safe, and sustainable (by design) ENMs. By embracing corona dynamics as a tool, not just a challenge, materials that perform their intended function and then degrade into benign byproducts at the end of their lifecycle can be designed. We anticipate that leveraging biomolecule-driven transformations will become a cornerstone of safe nanomaterial design, aligning innovation in nanotechnology with principles of environmental and human health protection.