Surface-modified protein microspheres capture amyloid-β and inhibit its aggregation and toxicity

Area of Science:

• Biomaterials Science
• Nanotechnology
• Neuroscience

Background:

• Protein microspheres offer biocompatibility and biodegradability for drug delivery.
• Targeting protein microspheres to specific cells or tissues remains a significant challenge.
• Alzheimer's disease (AD) is characterized by the aggregation of amyloid-beta (Aβ) peptides.

Purpose of the Study:

• To develop a facile method for covalently modifying protein microspheres for targeted delivery.
• To functionalize serum albumin microspheres with a peptide targeting amyloid-beta (Aβ).
• To evaluate the efficacy of these targeted microspheres in binding, sequestering, and mitigating Aβ toxicity.

Main Methods:

• A one-pot sonochemical approach was used for covalent modification of serum albumin microspheres.
• Microspheres were characterized using electron microscopy, dynamic light scattering, and confocal microscopy.
• Binding affinity and Aβ sequestration were assessed via fluorescence-activated cell sorting and Thioflavin-T assays; cellular toxicity was evaluated using PC12 cells.

Main Results:

• The modified microspheres demonstrated high affinity and selectivity for binding Aβ.
• The targeted microspheres effectively sequestered Aβ and reduced its aggregation into fibrillar structures.
• Conjugated microspheres reduced Aβ-induced toxicity in neuron-like PC12 cells.
• Modified microspheres exhibited enhanced stability and reduced size compared to unmodified ones.

Conclusions:

• A novel sonochemical method enables targeted covalent modification of protein microspheres.
• Peptide-conjugated albumin microspheres show significant potential for Aβ sequestration in Alzheimer's disease.
• These targeted microspheres represent a promising strategy for AD diagnostics and therapeutics.