Corona Dynamics of Nanoparticles and Their Functional Design Space in Molecular Sensing

As nanomaterials increasingly interact with complex biological environments, understanding and designing their interfacial layers is critical for enabling functional and responsive behaviors. The protein corona, a spontaneously formed biomolecular layer on the nanoparticle surface, plays a key role in determining biodistribution, cellular uptake, and immune recognition. In contrast, corona phase molecular recognition (CoPhMoRe), a synthetic sensing strategy based on noncovalent polymer adsorption, leverages programmable coronas to achieve selective molecular sensing through tunable fluorescence modulation. Although both systems exhibit similar interfacial behaviors rooted in molecular adsorption, their conceptual parallels have not been examined in an integrated framework. In this review, we present a comprehensive overview of how the protein corona has been redefined from a passive biological artifact to a functional interfacial layer, and how CoPhMoRe shares key conceptual principles through its use of programmable surface coronas for molecular recognition. We examine key advances in protein adsorption, functionalized-SWCNT interfaces, molecular sensing mechanisms, and machine learning-guided sensor construct design. Building on inspiration from the evolving concept of the protein corona, we propose future directions for CoPhMoRe as a programmable interfacial platform with expanding potential not only in molecular sensing but also in the development of personalized diagnostic and theranostic systems capable of responding to disease-specific molecular signatures. With its dynamic and adaptive interface, CoPhMoRe is expected to support ongoing developments in nanoscale diagnostics, precision medicine, and responsive nanotechnology.