Multifunctional Metal-Organic Framework as a Versatile Nanoplatform for Aβ Oligomer Imaging and Chemo-Photothermal Treatment in Living Cells

In view of the close association of β-amyloid oligomers (AβO) with the clinical development of Alzheimer's disease (AD) symptoms, it is urgent to design a promising sensing and therapeutic strategy that can target AβO for preventing or delaying the onset of AD. Herein, a core-shell nanocomposite CeONP-Res-PCM@ZIF-8/polydopamine (PDA) was synthesized through an in situ encapsulated strategy, in which resveratrol (Res), ceria nanoparticles (CeONPs), and PCM (tetradecanol) were embedded into the ZIF-8/PDA matrix via a water-based mild approach. Using the AβO aptamer, the ability of CeONP-Res-PCM@ZIF-8/PDA/Apt as the fluorescent sensing platform for AβO detection and intracellular imaging was demonstrated. The nanocomposite was high in Res loading (27.5%) and could be activated to release the encapsulated Res upon illumination with NIR through PCM regulation. Moreover, due to the synergetic interactions of PDA, CeONPs, and Res in one system, CeONP-Res-PCM@ZIF-8/PDA/Apt nanocomposites exhibited multifunctional effects on inhibiting Aβ aggregation, degrading Aβ fibrils, and alleviating Aβ-induced oxidative stress and neural Apoptosis. These therapeutic effects could be enhanced under NIR irradiation by virtue of the excellent photothermal property of PDA. As far as we know, there is no report of using ZIF-8-based Materials for simultaneous sensing and therapeutic applications. This work boosted the development of multifunctional nanoagents for biomedical research studies.