An in situ-triggered and chemi-excited photooxygenation system for Aβ aggregates

Abstract

Photooxygenation of Aβ protein has emerged as an effective and promising strategy against Alzheimer’s disease (AD). However, the penetration depth of excitation light into the skull and brain is limited, which restricts its further development. In this work, for the first time, we report an in situ-triggered and chemi-excited photooxygenation system capable of photooxygenating aggregated Aβ without the need for an external excitation source. A photosensitizer (BD-6-3) has been designed and synthesized that could mediate photooxidative degradation of Aβ aggregates under white light. BD-6-3 and bis[2,4,5-trichloro-6-(pentoxycarbonyl) phenyl] ester were loaded in mesoporous silica nanoparticles, which were in turn decorated with lactoferrin to afford the in situ-triggered and chemi-excited photooxygenation system Lf@6-3. It could be activated by the high concentration of H2O2 in the pathological microenvironment of AD to produce chemiluminescence. Singlet oxygen (1O2) produced can photooxygenate Aβ aggregates, thereby inactivating them and suppressing their neurotoxic effect.