A Hydroxyquinoline\nPolymer with Excellent Amyloidosis\nInhibition and Protein Delivery Ability to Combat Amyloid-β-Mediated\nNeurotoxicity

The accumulation of abnormal protein deposits known as\namyloid-β\n(Aβ) plaques contributes to the development and progression\nof Alzheimer’s disease. Aggregated Aβ exacerbates oxidative\nstress by stimulating the production of reactive oxygen species (ROS)\nin a detrimental feedback loop. 8-Hydroxyquinoline (8-HQ) is recognized\nfor its ability to inhibit or reverse Aβ aggregation and reduce\nneurotoxicity. Here, an 8-HQ-based polymer, DHQ, was developed to\ncombat Aβ-mediated neurotoxicity by delivering an antioxidant\nenzyme. DHQ efficiently delivers superoxide dismutase into targeted\ncells, thereby downregulating the intracellular ROS level. Additionally,\nthe polymer effectively inhibits the fibrillization of three proteins\ninvolved in fibrosis, β-lactoglobulin (BLG), insulin, and Aβ1-40,\nat nanomolar concentrations. Cell culture models demonstrated that\nDHQ reduces ROS levels induced by Aβ1-40 aggregation, rescuing\ncell viability and preventing apoptosis. Intracellular delivery of\nSOD further enhanced the ability to maintain the ROS homeostasis.\nThis polymer offers a multifaceted approach to treating diseases associated\nwith amyloidosis.