Construction of an endogenously activated nanoamplifier for high-sensitivity detection and multimodal bioimaging of Alzheimer's disease

Based on DNA hairpin structures, MnO₂ nanoflowers, and Tf-AuNCs, an endogenously-activated Tf-AuNC-DNA@MnO₂ multifunctional nanoamplifier was developed for the sensitive detection of microRNA-9 (miR-9) and efficient multimodal bioimaging in living HT-22 cells and brain tissues by two-photon near-infrared fluorescence imaging (TP-NIRFI), fluorescence lifetime imaging (FLIM), and magnetic resonance imaging (MRI). The Tf-AuNC-DNA@MnO₂ multifunctional nanoamplifier exhibits superior two-photon near-infrared (TP-NIR) properties and extended fluorescence lifetimes. Using an enzyme-free amplification technique, i.e., the hybridization chain reaction (HCR), this approach can detect miR-9 with high selectivity and sensitivity and a low limit of detection (LOD) of 396 pM. In the brain tissue of AD mice, TP-NIRFI achieved a penetration depth of 290 μm and enabled a clear distinction between wild-type and APP/PS1 transgenic mice. Moreover, MRI could monitor H₂O₂ that induced the activation of the multifunctional nanoamplifier in real time. More importantly, the Tf-AuNC-DNA@MnO₂ multifunctional nanoamplifier could monitor in real-time the dynamic changes of endogenous miR-9 induced by Aβ oligomers in HT-22 cells with multimodal imaging technology. Therefore, the Tf-AuNC-DNA@MnO₂ multifunctional nanoamplifier can provide a comprehensive and in-depth understanding of the occurrence and development of AD, offering a new method and a powerful tool for early diagnosis of the disease.