A stimuli-responsive polymer modified nanopore for measuring β-amyloid peptide and zinc ions in brains of live mice with Alzheimer's disease

Abstract

β-Amyloid peptide (Aβ) monomers and zinc ions (Zn²⁺) are closely related with Alzheimer's disease (AD). Sensitive and selective monitoring of Aβ monomers and Zn²⁺ in the cerebral nervous system can provide important insights into the pathological process of AD. Herein, we report the development of a single glass nanopore product based on a novel four-component stimuli-responsive copolymer for the recognition of both Aβ monomers and Zn²⁺. Introduction of Aβ monomers appeared to have induced a change in the conformation of the copolymer, with this change leading to a significant regulation of the ion flux within the nanopore channel. Benefiting from its capacity to form multiple hydrogen-bonding interactions, the developed nanopore product displayed good sensitivity and selectivity for Aβ monomers. In addition, carboxamidoquinoline with an alkoxyethylamino chain (AQZ) was incorporated into the copolymer chains for the detection of Zn²⁺ through coordination bonds. This method was found to be ultra-sensitive for Aβ monomers and Zn²⁺, with detection limits down to 0.1 pM and 0.1 nM. As a result, when combined with in vivo microdialysis, this remarkably performing glass nanopore was successfully utilized for evaluating Aβ monomer and Zn²⁺ levels in the cerebrospinal fluid (CSF) of live mice.