Gd-nanoparticles functionalization with specific peptides for ß-amyloid plaques targeting.

Area of Science:

• Nanotechnology-based diagnostics
• Biomolecular imaging
• Neurodegenerative disease research

Background:

• Amyloidoses involve extracellular deposition of amyloid fibrils with a cross-β structure.
• Current diagnosis is tedious, lacking early protein typing and discrimination between amyloid types.
• Existing neuroimaging methods like MRI and PET-CT lack specificity for different amyloid deposits.

Purpose of the Study:

• To develop and evaluate peptide-functionalized nanoparticles for selective amyloid fibril detection.
• To assess the capacity of these nanoparticles to discriminate between different amyloid proteins.
• To establish a potential minimally-invasive imaging tool for amyloidoses typing and early diagnosis.

Main Methods:

• Functionalization of gadolinium-based MRI nanoparticles (AGuIX) with amyloid-beta (Aβ)-specific peptides (LPFFD and KLVFF).
• Surface plasmon resonance (SPR) studies to assess binding affinities to Aβ(1-42) and mutated transthyretin (V30M-TTR) fibrils.
• Immunohistochemistry on Alzheimer's disease-like neuropathology brain tissue to evaluate in vivo targeting specificity.

Main Results:

• Functionalized nanoparticles showed specific interaction with Aβ(1-42) fibrils (Kd values of 403 and 350 µM) but not with V30M-TTR fibrils.
• [(11)C]PIB, a known amyloid marker, interacted with both Aβ(1-42) and V30M-TTR fibrils, confirming its non-specific binding.
• Immunohistochemistry confirmed that KLVFF- and LPFFD-grafted AGuIX nanoparticles selectively recognized and bound Aβ plaques in mouse brain tissue.

Conclusions:

• Peptide-functionalized AGuIX nanoparticles demonstrate selective targeting of Aβ amyloid fibrils.
• These nanoparticles show potential for discriminating between different types of amyloid deposits.
• This represents a significant step towards developing advanced multimodal imaging tools for diagnosing amyloidoses.