Peptide Based Covalent Organic Framework for the Magnetic Resonance Imaging‐Mediated Attenuation of Amyloid‐ β Fibrils

ABSTRACT The abnormal amyloid‐ β (A β ) aggregation is critical in the progression of Alzheimer's disease pathology, yet clinical therapeutics to alleviate amyloidosis in the patients is hindered due to low efficiency and side effects. Here, a multifunctional nanoplatform (Pep‐COF@E/P/S), where A β targeting peptide KLVFFA, small‐molecule EGCG and superparamagnetic iron oxide nanoparticles (SPIONs) were combined together upon the covalent organic framework to attenuate A β fibrils, alleviate A β fibrils‐induced cytotoxicity, and function as an MRI probe, is reported. Specifically, Pep‐COF@E/P/S enables A β targeting through the hydrogen bond of the KLVFFA component. Meanwhile, A β fibrils were attenuated by hydrogen bond and electrostatic interactions, thereby alleviating A β fibrils‐induced reactive oxygen species (ROS) and mitochondrial dysfunction as well as membrane damage further. In addition, Pep‐COF@E/P/S also exhibited favorable blood compatibility, biosafety as well as BBB permeability in vivo. Of note, the combination of SPIONs enables Pep‐COF@E/P/S as a potential MRI probe. It is expected that multifunctional Pep‐COF@E/P/S provides an attractive avenue to promote the development of precise and efficacious treatment of Alzheimer's disease.