A Near‐Infrared‐Controllable Artificial Metalloprotease Used for Degrading Amyloid‐β Monomers and Aggregates

摘要: Proteolysis of amyloid-β (Aβ) is a promising approach against Alzheimer's disease. However, it not feasible to employ natural hydrolases directly because their cumbersome preparation and purification, poor stability, hazardous immunogenicity. Therefore, artificial enzymes have been developed as potential alternatives hydrolases. Since specific cleavage sites Aβ are usually embedded inside the β-sheet structures that restrict access by enzymes, this strongly hinders efficiency for practical applications. Herein, we construct NIR (near-IR) controllable metalloprotease (MoS2 -Co) using molybdenum disulfide nanosheet ) cobalt complex 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Codota). Evidenced detailed experimental theoretical studies, NIR-enhanced MoS2 -Co can circumvent restriction simultaneously inhibition formation destroying preformed aggregates in living cell. Furthermore, our designed an easy graft Aβ-target agent prevents misdirected or undesirable hydrolysis reactions, has demonstrated cross blood brain barrier. This method be adapted other kinds amyloids.