Development of amyloid beta gold nanorod aggregates as optoacoustic probes

Abstract

Propagation of small amyloid beta (A{beta}) aggregates (or seeds) has been suggested as a potential mechanism of Alzheimers disease progression. Monitoring the propagation of A{beta} seeds in an organism would enable testing of this hypothesis and, if confirmed, provide mechanistic insights. This requires a contrast agent for long-term tracking of the seeds. Gold nanorods combine several attractive features for this challenging task, in particular, their strong absorbance in the infrared (enabling optoacoustic imaging) and the availability of several established protocols for surface functionalization. In this work, polymer-coated gold nanorods were conjugated with anti-A{beta} antibodies and specifically attached to pre-formed A{beta} seeds. The resulting complexes were characterized for their optical properties by UV/Vis spectroscopy and multispectral optoacoustic tomography. The complexes retained their biophysical properties, i.e. their ability to seed A{beta} fibril formation. They remained stable in biological media for at least 2 days and showed no toxicity to SH-SY5Y neuroblastoma cells up to 1.5 nM and 6 M of gold nanorods and A{beta} seeds, respectively. Taken together, this study describes the first steps in the development of probes for monitoring the spread of A{beta} seeds in animal models.