Improving Sensitivity and Specificity of Amyloid-beta Peptides and Tau Protein Detection with Antibiofouling Magnetic Nanoparticles for Liquid Biopsy of Alzheimer's Disease

• Type of Material: Article
• Authors: Yuancheng Li, Emory University; Esther Lim, Philadelphia College of Osteopathic Medicine–Georgia Campus; Travis Fields, Philadelphia College of Osteopathic Medicine–Georgia Campus; Hui Wu, Emory University; Yaolin Xu, Emory University; Andrew Wang Wang, Ocean Nanotech LLC; Hui Mao, Emory University
• Language: English
• Date: 2019-07-01
• Publisher: AMER CHEMICAL SOC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 American Chemical Society
• Final Published Version (URL): http://dx.doi.org/10.1021/acsbiomaterials.9b00086
• Title of Journal or Parent Work: ACS BIOMATERIALS SCIENCE & ENGINEERING
• Volume: 5
• Issue: 7
• Start Page: 3595
• End Page: 3605
• Grant/Funding Information: This study is supported in part by NIH grants (Grants U01CA198913, R01CA154846, and R01CA202846) to H.M.
• Keywords: CEREBROSPINAL-FLUID; FUTURE; Alzheimer's disease; Science & Technology; HUMAN PLASMA; Materials Science; amyloid-beta peptides; magnetic nanoparticles; Technology; Materials Science, Biomaterials; tau proteins; immunomagnetic separation; biofouling; BIOMARKERS

Abstract

Alzheimer's disease (AD) is a growing global healthcare burden affecting the aging population and society. Given the lack of effective treatment to AD, early detection at the prodromal stage and timely monitoring of changes during progression are considered the best approach to control and intervene in disease progression. "Liquid biopsy" of AD biomarkers amyloid-β peptides (Aβs) and tau proteins in the cerebrospinal fluid (CSF) or blood samples holds great promises for cost-effective, widely accessible, and easy-administrated noninvasive detection and follow-up of AD. However, current in vitro detection methods have not yet demonstrated sufficient sensitivity and specificity using neither Aβs nor tau proteins biomarkers. One major challenge of accurate detection and measurement of biomarker levels in biofluidic samples is the biofouling effect with nonspecific adsorption of unwanted biomolecules, such as various serum proteins, on the surface of targeted detecting agents or devices, causing false-positive and false-negative findings. In this study, antibiofouling polymer polyethylene glycol-block-allyl glycidyl ether (PEG-b-AGE) coated magnetic iron oxide nanoparticles (IONPs) capable of suppressing the nonspecific interactions with biomolecules, especially proteins, were investigated for the immunomagnetic capturing of Aβ40 and Aβ42 peptides and tau protein spiked in CSF- and serum-mimicking samples using corresponding antibodies conjugated as targeting ligands. Antibody-conjugated antibiofouling IONPs demonstrated improved specificity (>90%) and sensitivity (>95%) over those of antibody-conjugated magnetic micron beads (Dynabeads, ∼50% specificity and 30-40% sensitivity) widely used as magnetic separating agents under the same experimental conditions with the presence of nontargeted interfering proteins. The antibody-conjugated IONPs also exhibited significantly higher sensitivities (80-90%) and better performance of capturing Aβs and tau protein from the human whole blood samples than antibody-conjugated Dynabeads (∼20%).