Macrophage Membrane-Modified MoS₂ Quantum Dots as a Nanodrug for Combined Multi-Targeting of Alzheimer's Disease.

Abstract

The complex pathological mechanism of Alzheimer's disease (AD) limits the efficacy of simple drug therapy, and drugs are difficult to penetrate the blood-brain barrier (BBB). Therefore, it is a breakthrough to enhance the therapeutic effect of AD by rationally using multiple therapeutic strategies to inhibit multiple pathological targets. In this study, macrophage membrane (MM) with active targeting inflammation function is used to functionalize molybdenum disulfide quantum dots (MoS₂ QDs) with the properties of elimination of reactive oxygen species (ROS) and anti-Aβ_1-42 deposition to form the nano drug (MoS₂ QDs/MM), and play the role of multi-target combined therapy with NIR. The results show that MoS₂ QDs/MM has a targeted therapeutic effect on ROS elimination and anti-deposition of Aβ_1-42 . In addition, the combined therapy group effectively reduced Aβ_1-42 mediated cytotoxicity. The modification of MM could effectively target the brain, and NIR irradiation could actively increase the cross of BBB of materials. In vivo behavioral study also show that APP/PS1 mice in the combined treatment group showed the similar exploration desire and learning ability to mice in the group of WT. MoS₂ QDs/MM is an excellent nano drug with multiple effects, which has advantages in the field of neurological diseases with crisscross pathogenesis.