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

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.