Inhibition of metal-induced amyloid β-peptide aggregation by a blood–brain barrier permeable silica–cyclen nanochelator

Abstract

A BBB-passable nanoscale silica–cyclen chelator effectively reduces the metal-induced Aβ aggregates and related ROS, thereby decreasing the neurotoxicity of Aβ.

The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation

“…MPAs have also been used for chelating in situ metals: this strategy allows for modulating abnormal metal metabolism such as in Alzheimer's disease in which a high copper concentration triggers neuronal toxicity favoring the formation of pathogenic β‐amyloid plaques and reactive oxygen species (ROS). Derivatives of TACN, of cyclam and cyclen were studied, the latter being conjugated with the β‐sheet breaker KLVFF peptide or with silica nanoparticles …”

Front Cover: The Scope of Application of Macrocyclic Polyamines Beyond Metal Chelation (Eur. J. Org. Chem. 36/2019)

“…Derivatives of TACN, [64] of cyclam and cyclen [65] were studied, the latter being conjugated with the b-sheet breaker KLVFF peptide [66] or with silica nanoparticles. [67] MPAs have also been embedded as bioactive components per se, the most brilliant example being certainly AMD3100: [68] this bis-cyclam derivative is used as an antagonist of CXCR4 receptors, initially developed as an anti-HIV agent and subsequently repurposed for the mobilization of hematopoietic stem cells in cancer patients, now commercialized as Mozobil® (plerixafor). [69] AMD3100 was also studied for its ability to alter the copper metabolism in Alzheimer's disease (vide supra) [70] and as possible anti-malaria agent.…”

The Membrane Axis of Alzheimer's Nanomedicine

“…In addition to AuNPs, nanoceria, iron oxide nanoparticles, silicon dioxide nanoparticles, silver nanoparticles as well as transition‐metal nanomaterials such as molybdenum disulfide and black phosphorus have been shown as promising biocompatible nanomedicines for sequestering toxic amyloid species and alleviating their cell toxicity (Table 3). [ 148–155 ]…”

“…In addition to AuNPs, nanoceria, iron oxide nanoparticles, silicon dioxide nanoparticles, silver nanoparticles as well as transition-metal nanomaterials such as molybdenum disulfide and black phosphorus have been shown as promising biocompatible nanomedicines for sequestering toxic amyloid species and alleviating their cell toxicity (Table 3). [148][149][150][151][152][153][154][155] Polymeric nanocomposites possess versatile physicochemical properties, which can be utilized to render nanoparticle-biomolecular composites for biomedical applications. [156] By altering their lipid concentration and composition, polymethacrylatecopolymer (PMA) encased lipid-nanodiscs (%10 nm) effectively regulated Aβ fibrillization to exhibit less neurotoxicity.…”