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.
Yuxin Zheng,Limin Ma,Yu Wang,Jianshe Huang,Jianshan Ye,Xiurong Yang
Several different receptor candidates have been identified that bind monomeric, oligomeric, or fibrillar forms of amyloid-β (Aβ) protein, thus being involved in the clearance or cytotoxic action of Aβ. Component protein C1q, the initiator of the classical complement pathway, has been extensively reported to mediate neuroprotection or synapse loss through interactions with different effectors. Therefore, quantification of the C1q–Aβ interaction is a prerequisite for a better understanding of its implications in disease. Herein, we established a layer-by-layer interface sensing platform to precisely quantify the biomolecular interactions occurring between component C1q and amyloid-β protein 42 (Aβ42) in distinct morphological states. By leveraging the dual polarization interferometry (DPI) technique, we obtained real-time data pertaining to the mass, thickness, and density of the biomolecular layers during the binding process and calculated the binding dynamic parameters. From the in-depth analysis of the kinetic results and electrochemical verification, we determined that Aβ42 monomer (Aβ42M) exhibited a higher affinity for C1q than the Aβ42 oligomer (Aβ42O). This affinity could potentially account for the possibility that the C1q–Aβ42M interaction may be the first step to mediate the pivotal roles of C1q in Alzheimer’s disease (AD). This study provides a new perspective on the interaction between C1q and Aβ42, and it offers new information on the C1q-involved signaling pathway to advance our understanding of the molecular mechanism of AD.
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