Zeolite Nanoparticles Inhibit Aβ-Fibrinogen Interaction and Formation of Consequent Abnormal Structural Clot – ACS Applied Materials & Interfaces (ACS Publications)

ACS Appl. Mater. Interfaces, Just Accepted Manuscript

DOI: 10.1021/acsami.6b10941

EMT-type zeolite nanoparticles (EMT NPs) with diameter smaller than 12 nm and uniform pore size of 7.3 Å have shown high selective affinity toward plasma protein (fibrinogen). Besides, the EMT NPs have demonstrated no adverse effect on blood coagulation hemostasis. Therefore, it was envisioned that the EMT NPs could inhibit possible β-Amyloid (Aβ)-fibrinogen interactions that result in the formation of structurally abnormal clots, which are resistant to lysis, in cerebral vessels of patients with Alzheimer disease (AD). To evaluate this hypothesis, the clot formation and degradation of Aβ-fibrinogen in the presence and absence of the EMT zeolite NPs were assessed. The results clearly showed that the delay in clot dissolution was significantly reduced in the presence of zeolite NPs. By formation of protein corona, the EMT NPs showed a negligible reduction in their inhibitory strength. Docking of small molecules (Aβ-fibrinogen) introduced novel potential inhibitory candidate. The zeolite NPs showed similar inhibitory effects on binding of fibrinogen to both Aβ (25-35) and/or Aβ (1-42). This indicates that the inhibitory strength of these NPs is independent on Aβ sequence and it is suggested that the zeolite NPs adsorb fibrinogen and specifically obstruct their Aβ binding sites. Therefore, the zeolite NPs can be the safe and effective inhibitors in preventing Aβ-fibrinogen interaction and consequent cognitive damage.