MoS2 quantum dots based on lipid drug delivery system for combined therapy against Alzheimer's disease

Pathological pathways of Alzheimer's disease (AD) are criss-crossed, various pathological factors are dynamically correlated and relatively independent, which makes the single-target drug therapy less effective. Therefore, rational use of multiple therapeutic strategies for accurate inhibition of multiple pathological targets are effective to enhance the efficacy of AD therapy. The combination of drug loading and the excellent photothermal conversion property of nanocomposites is highly innovative to combat the two prominent pathological factors of Alzheimer's disease, oxidative stress and amyloid-β-(1–42) (Aβ1-42) deposition caused by reactive oxygen species (ROS) imbalance. Molybdenum disulfide quantum dots (MoS2 QDs) were selected as carriers and functionalized with lipids (MoS2 QDs/lipid) to improve their dispersibility in water, while effectively escaping immune clearance, improving the efficiency of multi-target applications and targeting advantages. The loading of curcumin (MoS2 QDs/lipid-Cur) not only overcomes the disadvantages of poor water solubility and low bioavailability of the drug, but also achieves the function of sustained release and long-term effect. MoS2 QDs/lipid-Cur showed excellent performance in the two therapeutic targets of anti-Aβ1-42 deposition and elimination of ROS in the early stage, and also obtained consistent excellent results in cell experiments. The drug-loaded combined with NIR treatment group significantly reduced Aβ1-42 mediated neurotoxicity. The in vivo photothermal experiment showed that NIR irradiation in the mouse brain can effectively open the blood-brain barrier (BBB) and increase the permeability of the material to the BBB. At the same time, NIR irradiation enriched drug-loaded material in the mouse brain, resulting in a significant increase in the temperature difference between the mice brains. MoS2 QDs/lipid-Cur is an excellent nanocomposite that integrates multiple functions and can be used for multi-target therapy.