Multifunctional porphyrin-substituted phenylalanine-phenylalanine nanoparticles for diagnostic and therapeutic applications in Alzheimer's disease.

Abstract

β-Amyloid (Aβ) peptides are believed as the diagnostic biomarkers and therapeutic targets of Alzheimer's disease (AD). Their complexes with copper ions can catalyze the generation of reactive oxygen species (ROS) to further promote neuronal death. Herein, we suggested that porphyrin-substituted phenylalanine-phenylalanine nanoparticles (TPP-FF NPs) could inhibit the aggregation of Aβ monomers, disassemble the fibrillar Aβ aggregates under light illumination, and depressing the Cu²⁺-induced generation of ROS. Meanwhile, the TPP-FF NPs could be used as the nanocarriers and quenchers of fluorescently-labeled probes for the detection of Aβ oligomer (AβO). Inhibition of Aβ assembly and dissolution of Aβ aggregates were monitored by Thioflavin T (ThT)-based fluorescent assay and characterized by atomic force microscopy. The Aβ/Cu²⁺-induced generation of ROS was limited by TPP-FF NPs. The fluorescein-labeled probe aptamers attached on the surface of TPP-FF NPs emitted low fluorescence. The interaction between AβO and aptamers induced the release of the probes from the surface of TPP-FF NPs, driving the fluorophore far away from the quenchers and turning on the fluorescence. The signal-on strategy can be used for the detection of AβO with a low detection limit. This work should be evaluable for the development of multifunctional candidates for the diagnosis and treatment of AD.