title: Surface-modified protein microspheres capture amyloid-β and inhibit its aggregation and toxicity.
abstract: 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-β (Aβ) 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 Aβ, sequester it from the medium and reduce its aggregation. Upon incubation with Aβ, the microspheres induced formation of amorphous aggregates on their surface with no apparent fibrillar structure. Moreover, the microspheres directly reduced the Aβ-induced toxicity toward neuron like PC12 cells. The conjugated microspheres are smaller than unmodified microspheres and remained stable throughout the incubation under physiological conditions.
authors: Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors: Michal
authors: M
authors: Richman
authors: Sarah
authors: S
authors: Wilk
authors: Natalia
authors: N
authors: Skirtenko
authors: Alex
authors: A
authors: Perelman
authors: Shai
authors: S
authors: Rahimipour
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D008854:Microscopy, Electron; D008863:Microspheres; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity*; D011485:Protein Binding; D051381:Rats; D012710:Serum Albumin, Bovine / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010455:Peptides; D012710:Serum Albumin, Bovine