Gold Nanocage-Based Dual Responsive Caged Metal Chelator Release System: Noninvasive Remote Control with Near Infrared for Potential Treatment of Alzheimer's Disease

Metal ions have been demonstrated to participate in the pathology of Alzheimer's disease (AD): amyloid- peptide (A) aggregation and formation of neurotoxic reactive oxygen species (ROS), such as H2O2. Metal chelator can block ROS formation and inhibit metal induced A aggregation. Metal-ion chelation therapy as a compelling treatment for AD has been extensively studied. However, most chelators are not suitable for AD treatment because of their poor permeability of the blood-brain barrier and their limited ability to differentiate toxic metals associated with A plaques from those associated with normal metal homeostasis. Here, a novel dual-responsive caged metal chelator release system based on gold nanocage (AuNC) for AD treatment is reported. Since arylboronic ester is redox- and thermal-sensitive, phenylboronic acid-functionalized AuNC can serve as an efficient delivery system for H2O2-responsive controlled release of metal chelator. The release can be further enhanced through remote control with NIR light because of the high near-infrared absorbance of AuNC. The smart system can effectively inhibit A aggregate formation, decrease cellular ROS, and protect cells from A-related toxicity. In light of these advantages, this design provides new insights into noninvasive remote control with NIR to improve therapeutic efficacy for treatment of Alzheimer's disease.