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

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.