Study of the Aggregation Behavior of Proteins Related to Neurodegenerative Diseases Based on the Photoluminescence of Perovskite Nanocrystals

Neurodegenerative diseases (NDs) are closely associated with abnormal protein aggregation. In this study, SiO₂-coated CsPbBr₃ nanocrystals (CPB NCs) were exploited as label-free photoluminescence (PL) probes to investigate the aggregation behavior of amyloid β (Aβ), a key protein in Alzheimer's disease. The PL intensity of the CPB NCs in both aqueous dispersion and thin-film states decreased with increasing degree of Aβ aggregation. The relative PL intensity could quantitatively distinguish the aggregation states of Aβ, and the sensitivity of the thin-film system was twice that of the aqueous dispersion. This approach innovatively enabled the preliminary monitoring of protein aggregates without interfering with the aggregation process while avoiding the effects of reactive oxygen species generated during the aggregation and metal ions themselves on PL signals. Through threshold segmentation, the relative fluorescence intensity was further used to distinguish small-molecule drugs with disaggregation effects (ratio > 0.5) from those without (ratio ≈ 0). Based on a series of experiments, the photoinduced electron transfer mechanism was proposed to explain the change in the PL signal. Due to the electrostatic interaction between CPB NCs and proteins, this probe had potential for studying the aggregation states of other proteins (such as α-synuclein) related to NDs. Overall, this work offered new insights into the application of metal halide perovskites in biosensing as well as for the diagnosis and drug screening of NDs.