Surface-Modified Protein Microspheres Capture Amyloid-[beta] and Inhibit its Aggregation and Toxicity

• Published in: Chemistry : a European journal 2011-09, Vol.17 (40), p.11171
• Main Authors: Richman, Michal, Wilk, Sarah, Skirtenko, Natalia, Perelman, Alex, Rahimipour, Shai
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Chemistry; Microscopy; Proteins; Toxicity
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201101326

The biocompatible and biodegradable properties of protein microspheres and the recent advances in their preparation have generated considerable interest of utilizing these core-shell structures for drug delivery and diagnostic applications. However, effective targeting of protein microspheres to desirable cells or loci still remains a challenge. Here, we describe for the first time a facile one-pot sonochemical approach for covalent modification of protein microspheres made from serum albumin; the surface of which is covalently decorated with a short recognition peptide to target amyloid-[beta] (A[beta]) as the main pathogenic protein in Alzheimer's disease (AD). The microspheres were characterized for their morphology, size, and entrapment efficacy by electron microscopy, dynamic light scattering and confocal microscopy. Fluorescence-activated cell-sorting analysis and Thioflavin-T binding assay demonstrated that the conjugated microspheres bind with high affinity and selectivity to A[beta], sequester it from the medium and reduce its aggregation. Upon incubation with A[beta], the microspheres induced formation of amorphous aggregates on their surface with no apparent fibrillar structure. Moreover, the microspheres directly reduced the A[beta]-induced toxicity toward neuron like PC12 cells. The conjugated microspheres are smaller than unmodified microspheres and remained stable throughout the incubation under physiological conditions.