Disposable immunoplatforms for the simultaneous determination of biomarkers for neurodegenerative disorders using poly(amidoamine) dendrimer/gold nanoparticle nanocomposite

Abstract

Early diagnosis in primary care settings can increase access to therapies and their efficiency as well as reduce health care costs. In this context, we report in this paper the development of a disposable immunoplatform for the rapid and simultaneous determination of two protein biomarkers recently reported to be involved in the pathological process of neurodegenerative disorders (NDD), tau protein (tau), and TAR DNA-binding protein 43 (TDP-43). The methodology involves implementation of a sandwich-type immunoassay on the surface of dual screen-printed carbon electrodes (dSPCEs) electrochemically grafted with p-aminobenzoic acid (p-ABA), which allows the covalent immobilization of a gold nanoparticle-poly(amidoamine) (PAMAM) dendrimer nanocomposite (3D-Au-PAMAM). This scaffold was employed for the immobilization of the capture antibodies (CAbs). Detector antibodies labeled with horseradish peroxidase (HRP) and amperometric detection at − 0.20 V (vs. Ag pseudoreference electrode) using the H 2 O 2 /hydroquinone (HQ) system were used. The developed methodology exhibits high sensitivity and selectivity for determining the target proteins, with detection limits of 2.3 and 12.8 pg mL −1 for tau and TDP-43, respectively. The simultaneous determination of tau and TDP-43 was accomplished in raw plasma samples and brain tissue extracts from healthy individuals and NDD-diagnosed patients. The analysis can be performed in just 1 h using a simple one-step assay protocol and small sample amounts (5 μL plasma and 2.5 μg brain tissue extracts).

Electrochemical Biosensors Based on Nanomaterials for Early Detection of Alzheimer’s Disease

“…In a similar approximation, Tau protein was detected by Serafin et al [ 179 ] in combination with TAR DNA binding protein 43 (TDP-43), a protein involved in the evolution of several neurodegenerative diseases that has been found to form deposits in AD [ 180 ]. In this biosensor, AuNPs combined with PAMAM were used as scaffolds for the immobilization of antibodies to dual SPCEs, while HRP functionalized with antibodies was used for the amperometric detection of AD biomarkers using H 2 O 2 / hydroquinone system as reporter, providing a LOD of 50 fM for tau-441 and 0.287 pM for TDP-43.…”

Nanomedicine: A Promising Way to Manage Alzheimer’s Disease

“…Co-administration of tacrine with both generation 4.0 and polyamidoamine dendrimers as nanocomposites has also been used to enhance the biocompatibility and reduce the toxicity of drugs used for the therapy of AD (Igartúa et al, 2020). Furthermore, the nanocomposites of poly(amidoamine) dendrimer and gold NPs have been used to design the disposable immunoplatforms for simultaneous determination of the biomarkers for AD (Serafín et al, 2020).…”

Electrochemical sensing of blood proteins for mild traumatic brain injury (mTBI) diagnostics and prognostics: towards a point-of-care application

“…using free and alkaline phosphatase (ALP)-labelled target molecules for detection of GM-CSF biomarker 175 ) or, more commonly, sandwich assay (e.g. horseradish peroxidase (HRP)-labelled microuidic bead-based enzyme-linked immunosorbent assay for detection of IL-6 176 or Tau proteins 177,178 ). A peculiar dual-probe sandwich-like assay with a single incubation step has been suggested by Akhtar et al 136 for relatively rapid (ca.…”