NIR-excited upconversion nanoparticles used for targeted inhibition of Aβ42 monomers and disassembly of Aβ42 fibrils

Much attention has been paid to oxidising amyloid-β peptides (Aβ) for inhibiting their aggregation using photosensitive materials. However, the low penetration of ultraviolet/visible light into biological tissues and low targeting properties of the materials hinder their application. Here, we constructed a novel platform for attenuating the neurotoxicity of Aβ through functional upconversion nanoparticles (UCNPs@SiO₂-ThS). UCNPs@SiO₂-ThS can not only inhibit the aggregation of Aβ₄₂ monomers, but also disassemble Aβ₄₂ fibrils by its selective photooxidative capacity under the irradiation of near-infrared (NIR) light. Moreover, based on the enhancement of ThS fluorescence after attaching to Aβ₄₂ fibrils, only Aβ₄₂ fibrils exposed to both UCNPs@SiO₂-ThS and light can be oxidized rather than other normal proteins. To further enhance Aβ-target photooxygenation, we introduced the Aβ-target peptide (KLVFF) on the surface. Compared to traditional chemotherapies and radiotherapies, this novel PDT strategy shows remarkably reduced side effects and improved targeting.