A novel AD theranostic platform with NIR-II laser controlled drug release and real-time monitoring of therapeutic outcomes

There is a long-standing lack of monitoring of Alzheimer's disease (AD) treatment. Imaging-guided dynamic monitoring of neurological disease treatment can provide a basis for sustained treatment, reflecting the outcomes of treatment and guiding the adjustment of therapy strategies. Here, by ingeniously using a second near-infrared (NIR-II) laser twice in tandem, we designed an AD theranostic nanoplatform with real-time monitoring of AD therapeutic outcomes. Upon first being irradiated with a 1064 nm laser, it realizes the light-controlled delivery of nanoparticles for valid antioxidant therapy. Notably, with secondary irradiation, the presence of AβO and Ca2+ triggered the DNA nanomachine, causing the fluorescent signal to recover. Using a two-step series switch based on thermodynamics, the platform can not only differentiate AD mice from wild-type mice but also provide guidance for the treatment of AD via monitoring the degree of intracellular calcium overload in the brain. Results suggest that the degree of calcium overload is negatively correlated with treatment outcome and can be used as a prognostic indicator for precision medicine. This method provides an image-based non-invasive strategy for early prognosis prediction of AD treatment, which is helpful for future precision medicine treatment planning and prognosis stratification.