Polymer-lipid hybrid nanoparticles co-encapsulating fucoxanthin and carbon dots for targeted anti-inflammatory therapy in Alzheimer´s disease

Abstract

Alzheimer´s disease (AD) is a long-term brain disorder characterized by the buildup of proteins like amyloid-beta (Aβ) and Tau. This disease process can start up to 20 years before symptoms such as memory loss, language problems, changes in personality, and eventually dementia appear. Currently, AD has no cure, and available treatments only ease symptoms, making it a major global health concern. Developing new therapies is urgently needed. Nanomedicine presents promising solutions, especially for overcoming challenges like delivering drugs across the blood-brain barrier (BBB). In this study, we explored polymer-lipid hybrid nanoparticles (NPs) decorated with transferrin (Tf) to help them cross the BBB. These NPs were loaded with carbon dots (CDs) and fucoxanthin (Fx), which have antioxidant and anti-inflammatory qualities that may benefit neurodegenerative disease treatment. The resulting nanoparticle formulation (NPs-CDFx) had encapsulation efficiencies of 45% for Fx and 10% for CDs, with an average particle size of about 88.74 nm. The safety of these NPs was tested using an in vitro model with lipopolysaccharide (LPS) stimulated rat astrocytes, where high cell viability (92.18%) was observed. qPCR analysis showed that NPs-CDFx significantly lowered the expression of genes linked to neuroinflammation and disease progression, such as APP, GFAP, and S100β. To further confirm delivery, the NPs were injected into five-day-old zebrafish larvae, where confocal microscopy detected the CDs' fluorescence in the brain, indicating successful targeted delivery across the BBB. Overall, these findings suggest that the nanoparticles can efficiently deliver therapeutic agents to the brain, reduce neuroinflammatory gene expression, and demonstrate the effectiveness of polymer-lipid hybrid nanoparticles for targeted brain drug delivery.