A significant pathological signature of Alzheimer's disease (AD) is the deposition of amyloid-β (Aβ) plaques in the brain and the synaptic dysfunction and neurodegeneration associated with it. Compounds or drugs that inhibit Aβ fibrillation are thus desirable to develop novel therapeutic strategies against AD. Conventional strategies usually require an elaborate design of their molecular structures. Here we report the size-effect of gold nanoparticles (AuNPs) and nanoclusters (AuNCs) in the inhibition of protein amyloidosis. Using L-glutathione stabilized AuNPs with different sizes and AuNCs as examples, we show that large AuNPs accelerate Aβ fibrillation, whereas small AuNPs significantly suppress this process. More interestingly, AuNCs with smaller sizes can completely inhibit amyloidosis. Dynamic light scattering (DLS) experiments show that AuNCs can efficiently prevent Aβ peptides from aggregation to larger oligomers (e.g. micelles) and thus avoid nucleation to form fibrils. This is crucially important for developing novel AD therapies because oligomers are the main source of Aβ toxicity. This work presents a novel strategy to design anti-amyloidosis drugs, which also provides interesting insights to understand how biological nanostructures participate in vivo in Aβ fibrillation from a new perspective.

Gold nanoclusters (AuNCs) have become a promising material for bioimaging detection because of their tunable photoluminescence, large Stokes shift, low photobleaching, and good biocompatibility. Last decade, great efforts have been made to develop AuNCs for enhanced imaging contrast and multimodal imaging. Herein, an updated overview of recent advances in AuNCs was present for visible fluorescence (FL) imaging, near-infrared fluorescence (NIR-FL) imaging, two-photon near-infrared fluorescence (TP-NIR-FL) imaging, computed tomography (CT) imaging, positron emission tomography (PET) imaging, magnetic resonance imaging (MRI), and photoacoustic (PA) imaging. The justification of AuNCs applied in bioimaging mentioned above applications was discussed, the performance location of different AuNCs were summarized and highlighted in an unified parameter coordinate system of corresponding bioimaging, and the current challenges, research frontiers, and prospects of AuNCs in bioimaging were discussed. This review will bring new insights into the future development of AuNCs in bio-diagnostic imaging.

The misfolding of amyloid-β (Aβ) peptides from the natural unfolded state to β-sheet structure is a critical step, leading to abnormal fibrillation and formation of endogenous Aβ plaques in Alzheimer's disease (AD). Previous studies have reported inhibition of Aβ fibrillation or disassembly of exogenous Aβ fibrils in vitro. However, soluble Aβ oligomers have been reported with increased cytotoxicity; this might partly explain why current clinical trials targeting disassembly of Aβ fibrils by anti-Aβ antibodies have failed so far. Here we show that Au₂₃(CR)₁₄ (a new Au nanocluster modified by Cys-Arg (CR) dipeptide) is able to completely dissolve exogenous mature Aβ fibrils into monomers and restore the natural unfolded state of Aβ peptides from misfolded β-sheets. Furthermore, the cytotoxicity of Aβ₄₀ fibrils when dissolved by Au₂₃(CR)₁₄ is fully abolished. More importantly, Au₂₃(CR)₁₄ is able to completely dissolve endogenous Aβ plaques in brain slices from transgenic AD model mice. In addition, Au₂₃(CR)₁₄ has good biocompatibility and infiltration ability across the blood–brain barrier. Taken together, this work presents a promising therapeutics candidate for AD treatment, and manifests the potential of nanotechnological approaches in the development of nanomedicines.