Engineering Nano-Bio Interfaces from Nanomaterials to Nanomedicines

CONSPECTUS: The nano-bio interface refers to the physical interface between the biological system and nanoscale surface topography, functioning as the barrier between two phases where critical reactions occur. In the last two decades, advances in nanofabrication techniques have heralded a new research area utilizing precisely engineered surfaces and structures to control cell cycles, pathways of metabolism, immune responses, and so forth. At the cellular level, engineered nanomaterials (ENMs) with typical surfaces and structures have been shown to actively affect biological responses, such as stimulating macrophage polarization, monitoring reduction-oxidation equilibrium, and manipulating protease activities via tunable nano-bio interactions. In this Account, we outline our recent progress in surface engineering and structural engineering to improve nano-bio interactions and the performance of nanomedicine. To regulate nanomaterial-molecule and nanomaterial-membrane interactions, we summarize the classical types of nano-bio interaction, extract the essential parameters in nanomaterial surface engineering and structural engineering, and propose effective techniques of surface engineering and structural engineering. We start with identifying the types of dominant interactions between nanomedicines and vital biomolecules: nanonucleic acids, nanoproteins, and nanomembranes. The surface engineering strategies of nano-bio interface tailoring are then arranged into four perspectives: the protein corona (the two modes of protein corona formation and their impacts on altering the affinity profiles of nanomaterials to biological systems), thermoresponsive polymers in superficial modification (passive activation by in situ gelation and active regulation by photothermal conversion), stimulus-induced bonding groups (mediation of nanoparticle aggregation to balance the penetration depth and longterm retention), and inherent surface properties (surface roughness for maximized nano-bio adhesion, surface charge for electrostatic attraction and biological barrier penetration of nanoparticles, and skeleton oxidation to boost nano-bio hydrogen bonding). Structural engineering of nanomaterials occurs by remote manipulation through electron-transfer facilitation (doping, heterojunction, defects, and vacancies) of the nano-bio interaction, following multifaceted solutions that combine multiple surface engineering plans. The scopes and limitation section discusses the prospective problems that can occur when nanomaterials/ nanomedicines interact in biological contexts. Because both clinical and laboratory studies have shown the influence of surface topological features on biological responses, the feedback of biological systems to different topographical features of nanomaterials/ nanomedicines is essential for us to comprehend the nano-bio interface at the relevant nanometer length scale. For on-demand nano-bio interactions, the discovery provides insight into the rational design of nanomaterials/nanomedicines.