BDNF Loaded Amino Acid‐Catecholamine Hybrid Nanoparticles as Curative Agents Against Cognitive Decline in Alzheimer's Disease

Abstract Alzheimer's disease (AD) is marked by the buildup of neurotoxic Aβ plaques.In this study, EGCG‐dopamine‐tryptophan nanoparticles (EDTNPs) that prevent Aβ fibrillization, aid plaque clearance, improve oxidative balance, reduce neuronal damage, and enhance cell survival through protective effects are synthesized. To boost neuroprotection further, BDNF, a neurotrophic factor that promotes neuronal growth, are loaded onto the EDTNPs (B‐EDTNPs), leading to a notable increase in the protection of neuronal cells. B‐EDTNPs exhibit a pronounced neuroprotective effect against FF and Aβ (1‐42) fibril‐induced toxicity in SH‐SY5Y neuroblastoma cells, enhancing cell viability from ≈ 37% to 92% and from 48% to 88%, respectively; which is ≈20% and ≈21% higher compared to EDTNPs at 24 h duration. Studies involving animal models further demonstrate that B‐EDTNPs effectively dislodge amyloid aggregates in vivo, leading to a significant reduction in plaque accumulation ( p < 0.001). This intervention not only promotes the clearance of toxic aggregates but also noticeably suppresses the NF‐κB and TNF‐α inflammatory biomarkers, aiding in restoring cognitive function and enhancing behavioral outcomes in treated BALB/c AD animal models. The theoretical studies show that NP components interact with Aβ (1–42) polypeptides, promoting disaggregation. This highlights a novel approach for creating effective nanocomposites that combine Aβ inhibitors with antioxidants to target AD.