Galactosylated Nanoparticles: Redefining Sugar-Driven Mechanisms in SERS, Metabolism, and Immune Modulation.

Galactosylated nanoparticles (Gal-NPs) are a new class of nanoplatforms linking molecular recognition, materials, and biomedical functions. This Review presents a galactose-centered framework in which galactose serves as a bioactive motif that influences nano-bio interactions and cellular responses. We present synthetic strategies-such as in situ polymerization, bridge conjugation, and carbonization-that enable controlled galactose display on organic and inorganic nanostructures, addressing the heterogeneity and scalability issues of traditional methods. Surface-displayed galactose may promote multivalent receptor binding, metabolic changes, and immune reprogramming, especially macrophage repolarization via ROS pathway. Importantly, integration with inorganic nanocores transforms galactose from a passive biomolecular ligand into a functionally traceable entity: plasmonic and magnetic components enable optical (e.g., SERS) and imaging (e.g., MRI) readouts, allowing real-time monitoring of galactose-mediated targeting, accumulation, and immunomodulation in biological systems. Combining biological activity with signal transduction, galactosylated nanohybrids become programmable systems for recognition, intervention, and imaging. This Review sees galactosylated nanoparticles as a versatile platform for next-generation theranostics.