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.