Clioquinol-Loaded UiO-66(Ce) Metal-Organic Frameworks for Dual Reactive Oxygen Species Scavenging and Metal Chelation in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a major neurodegenerative disorder associated with amyloid-β (Aβ) aggregation and oxidative stress, often linked to metal ion dyshomeostasis. In this study, we developed a clioquinol (CQ)-loaded UiO-66(Ce), a cerium-based metal-organic framework (MOF), as a potential dual-functional platform. The system is designed to combine reactive oxygen species (ROS) scavenging via Ce(III)/Ce(IV) redox cycling with the metal-chelating capability of CQ, aiming to modulate multiple AD-related pathological factors. The material was synthesized and characterized, and its biological performance was preliminarily evaluated in PC-12 cells using an Aβ-Cu2+ model system. The results suggest that UiO-66(Ce)-CQ exhibits acceptable biocompatibility and is associated with reduced intracellular ROS levels, improved cell viability, and modulation of Aβ aggregation behavior. Compared with its individual components, UiO-66(Ce)-CQ showed enhanced overall performance under the tested conditions. While this study is limited to initial in vitro evaluation, the findings provide a preliminary proof of concept for integrating ROS-scavenging and metal-chelating functionalities within a single MOF-based platform, which may offer a potential strategy for AD-related applications.