Biocatalytic ZIF-8 surface-functionalized micromotors navigating in the cerebrospinal fluid: toward Alzheimer management

Abstract

Alzheimer's disease (AD) is the major cause of irreversible dementia in the elderly population worldwide and one of the major causes of the decrease in the quality of life. Efficient diagnosis and monitoring would allow a fast treatment to delay the appearance of symptoms. Herein, zeolitic imidazole framework (ZIF-8)@Au@catalase micromotors are described for motion-based sensing of copper as a marker of AD. The synthesis design was based on enzyme covalent immobilization instead of encapsulation to maximize the contact with the sample at the microscale for the potential use of extremely low AD-diagnosed sample volumes. The micromotors are prepared by asymmetric modification of ZIF-8 with a gold layer for functionalization of catalase as a compatible biocatalyst. The micromotors can propel at speeds of up to 287 ± 41 μm s⁻¹ in cerebrospinal fluid (CSF) samples of healthy volunteers. Yet, in the presence of copper, catalase poisoning results in a decrease in the speed that can be monitored for motion-based sensing detection, as illustrated in the analysis of CSF samples from AD patients from mild to severe stages (Braak III to Braak VI). The copper-mediated modulation of catalase activity proposed here as an indicator of progression states in AD disease possesses distinct advantages such as ultrafast analysis (less than 1 min) and requiring only 1 μL of sample, holding considerable promise as a supporting prescreening tool for fast diagnosis of AD and other neurodegenerative diseases.