One of the key pathological features of Alzheimer’s disease (AD) is the existence of extracellular deposition of amyloid plaques formed with misfolded amyloid-β (Aβ). The conformational change of proteins leads to enriched contents of β sheets, resulting in remarkable changes of vibrational spectra, especially the spectral shifts of the amide I mode. Here, we applied stimulated Raman scattering (SRS) microscopy to image amyloid plaques in the brain tissue of an AD mouse model. We have demonstrated the capability of SRS microscopy as a rapid, label-free imaging modality to differentiate misfolded from normal proteins based on the blue shift (~10 cm⁻¹) of amide I SRS spectra. Furthermore, SRS imaging of Aβ plaques was verified by antibody staining of frozen thin sections and fluorescence imaging of fresh tissues. Our method may provide a new approach for studies of AD pathology, as well as other neurodegenerative diseases associated with protein misfolding.

Amyloid deposits are implicated in the pathogenesis of many neurodegenerative diseases such as Alzheimer's disease (AD). The inhibition of β-sheet formation has been considered as the primary therapeutic strategy for AD. Increasing data show that nanoparticles can retard or promote the fibrillation of amyloid-β (Aβ) peptides depending on the physicochemical properties of nanoparticles, however, the underlying molecular mechanism remains elusive. In this study, our replica exchange molecular dynamics (REMD) simulations show that fullerene nanoparticle – C₆₀ (with a fullerene : peptide molar ratio greater than 1 : 8) can dramatically prevent β-sheet formation of Aβ(16–22) peptides. Atomic force microscopy (AFM) experiments further confirm the inhibitory effect of C₆₀ on Aβ(16–22) fibrillation, in support of our REMD simulations. An important finding from our REMD simulations is that fullerene C₁₈₀, albeit with the same number of carbon atoms as three C₆₀ molecules (3C₆₀) and smaller surface area than 3C₆₀, displays an unexpected stronger inhibitory effect on the β-sheet formation of Aβ(16–22) peptides. A detailed analysis of the fullerene–peptide interaction reveals that the stronger inhibition of β-sheet formation by C₁₈₀ results from the strong hydrophobic and aromatic-stacking interactions of the fullerene hexagonal rings with the Phe rings relative to the pentagonal rings. The strong interactions between the fullerene nanoparticles and Aβ(16–22) peptides significantly weaken the peptide–peptide interaction that is important for β-sheet formation, thus retarding Aβ(16–22) fibrillation. Overall, our studies reveal the significant role of fullerene hexagonal rings in the inhibition of Aβ(16–22) fibrillation and provide novel insight into the development of drug candidates against Alzheimer's disease.

A new method to image drug release from drug–nanoparticle composites in living cells was established. The composites of silica coated gold nanorods (AuNR@SiO₂) and chlorine e6 (Ce6) photosensitizers (AuNR@SiO₂–Ce6) were formed by electrostatic force with a Ce6 loading efficiency of 80%. The strong resonance absorptions of AuNR@SiO₂–Ce6 in the near-infrared (NIR) region enabled the effective release of Ce6 from AuNR@SiO₂–Ce6 by 780 nm CW laser irradiation. The 780 nm laser beam was applied to not only control the releasing amount of Ce6 from cellular AuNR@SiO₂–Ce6 by adjusting the irradiation dose (time), but also to spatially confine the Ce6 release in cells by focusing the laser beam on the target sites. Furthermore, the fluorescence lifetime of Ce6 was found to change drastically from 0.9 ns in the AuNR@SiO₂–Ce6 complex to 6 ns after release, and therefore fluorescence lifetime imaging microscopy (FLIM) was introduced to image the photo-induced Ce6 release in living cells. Finally, the controllable killing effect of photodynamic cancer therapy (PDT) using AuNR@SiO₂–Ce6 was demonstrated by changing the released amount of Ce6, which indicates that AuNR@SiO₂–Ce6 is promising for targeted tumour PDT.

C60(OH)₂₄inhibits hIAPP aggregation by suppressing the fibril-prone structure and destabilizes hIAPP protofibrils by binding to the amyloid core region.