Pathological BBB Crossing Melanin-Like Nanoparticles as Metal-Ion Chelators and Neuroinflammation Regulators against Alzheimer’s Disease  

作　　者：Qianqian Huang Chaoqing Jiang Xue Xia Yufan Wang Chenxing Yan Xiaorong Wang Ting Lei Xiaotong Yang Wenqin Yang Guo Cheng Huile Gao 

机构地区：[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,West China School of Pharmacy,Sichuan University,Chengdu 610041,P.R.China [2]Laboratory of Molecular Translational Medicine,Center for Translational Medicine,Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University),Ministry of Education,Department of Pediatrics,West China Second University Hospital,Sichuan University,Chengdu 610041,P.R.China

出　　处：《Research》2024年第1期687-706,共20页研究（英文）

基　　金：the Research and Development Program of Science and Technology Department of Sichuan Province(2022JDJQ0050);111 Project(B18035);the Fundamental of Research Funds for the Central Universities.

摘　　要：Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD progression.Herein,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of AD.In this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβhitchhiking.In vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB crossing.The engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.

关 键 词：oxidative aggregation CHELATING 

分 类 号：R749.16[医药卫生—神经病学与精神病学]