An innovative approach to increasing the signal from fluorophores using plasmonic gold nanoparticles (surface-enhanced fluorescence effect) improved the detection of Aß aggregates in C. elegans and mouse models of Alzheimer’s disease.Age-related diseases like Alzheimer’s are increasingly prevalent and could affect over 130 million by 2050. During the aging process, overproduction of beta-amyloid (Aβ) peptides leads to the formation of different types of aggregates in the brain. While advanced stages of Alzheimer’s disease, when significant neurological degeneration is evident, are characterized by insoluble amyloid aggregates – known as senile plaques, Aβ peptides could serve as biomarkers for early diagnosis and monitoring.
Although Aβ aggregates labelled with a radioactive probe can be detected using positron emission tomography, the approach is expensive and of limited accessibility to most patients. A simpler means of detecting Aβ peptides or aggregates in vivo would be a very attractive alternative, particularly for early diagnosis. Now researchers believe they may have found a way to do just this [Cabrera et al., Nanomedicine 44 (2022) 102569, https://doi.org/10.1016/j.nano.2022.102569].
“We used gold nanoparticles combined with a fluorescence dye to improve the in vivo detection of Aβ insoluble and soluble aggregates,” explains Marcelo J. Kogan of the Universidad de Chile, who led the team from the Advanced Center for Chronic Diseases in Santiago, Pontificia Universidad Católica de Chile, Universidad Andres Bello, and Universidad Mayor with Rebeca Aldunate of Universidad Santo Tomás. “Moreover, gold nanoparticles can be strategically modified to deliver molecules that could regulate the toxicity of Aβ.”
The team recently developed a strategy for detecting Aβ aggregates in vivo using computed tomography and gold nanorods functionalized with peptides. Now, they have combined this strategy with Aβ-amyloid imaging probes based on curcuminoid molecules that fluoresce in the near-infrared (NIR). Gold nanoparticles boost the signal from these Aβ-amyloid probes via a surface enhanced fluorescence (SEF) effect because of their localized surface plasmon resonance (LSPR). The fluorophores are excited directly by incoming light and by that scattered from the nanoparticles.
“Our innovative approach allows in vivo detection of Aβ with high sensitivity,” says Kogan. “This system may contribute to the early diagnosis of Alzheimer’s disease and distinguish it from other types of dementia.”
The researchers demonstrate the potential of the approach in two animal models of the disease that overexpress the human Aβ peptide, nematode worms (C. elegans) and mice. The administration of targeted gold nanorods, along with or shortly before in vivo fluorescent probes, improves the sensitivity to and detection of Aβ-amyloids. The nanosystem with the NIR fluorescent probe could also be used for photothermal applications, such as breaking up the amyloid aggregates to reduce their toxicity.