Theranostic Nanoparticles for Fluorosensitive Visualization and Inhibition of Amyloid Beta‐Induced Neuroinflammation

ABSTRACT The emerging field of microglial therapies has significant potential to alleviate fibrillar amyloid beta (fAβ)‐associated neuroinflammation, which exacerbates neurodegeneration in Alzheimer's disease (AD). New therapeutic strategies integrate with diagnostic capabilities to robustly elucidate the mechanisms and consequences of intervention. Amphiphilic macromolecules (AMs), comprising a hydrophilic sugar backbone, hydrophobic aliphatic side chains, and poly(ethylene glycol) (PEG) segments for enhanced stability, exhibit significant potential for biomedical applications due to their biocompatibility and self‐assembled nanoscale structures. This study presents rhodamine B‐tagged (Rh) AMs (Rh‐AMs) that create stable nanoparticles (Rh‐AM‐NPs) with potential neurotherapeutic and diagnostic applications. Rh‐AMs were successfully synthesized and validated using NMR, FTIR, UV–vis, and fluorescent spectroscopy. The ratio of labeled to unlabeled AMs necessary for Rh‐AM‐NPs formation was optimized via flash nanoprecipitation to confirm the minimum quantity required for direct visualization within cells. Using an in vitro BV2 microglial model, we demonstrated that Rh‐AM‐NPs exhibit multifunctional properties, suppressing the microglial inflammatory response and reducing microglial uptake of fAβ within a low‐toxicity range, while simultaneously enabling in situ tracking of cellular interactions. This work validates a novel nanoplatform for combined AD therapy and diagnostics.