Multilayered Bioorthogonal SERS Nanoprobes Selectively Aggregating in Human Fluids: A Smart Optical Assay for ?-Amyloid Peptide Quantification

Year: 2023

Authors: Dallari C., Lenci E., Trabocchi A., Bessi V., Bagnoli S., Nacmias B., Credi C., Pavone FS.

Autors Affiliation: European Lab Nonlinear Spect LENS, I-50019 Sesto Fiorentino, Italy; Univ Florence, Dept Phys, I-50019 Sesto Fiorentino, Italy; Natl Res Council CNR, Natl Inst Opt INO, I-50019 Sesto Fiorentino, Italy; Univ Florence, Dept Chem, I-50019 Sesto Fiorentino, Italy; Univ Florence, Dept Neurol & Psychiat Sci NeuroFarba, I-50134 Florence, Italy; IRCCS Fdn Don Carlo Gnocchi, I-50143 Florence, Italy.

Abstract: Alzheimer’s disease (AD) is a debilitating neurological condition characterized by cognitive decline, memory loss, and behavioral skill impairment, features that worsen with time. Early diagnosis will likely be the most effective therapy for Alzheimer’s disease since it can ensure timely pharmacological treatments that can reduce the irreversible progression and delay the symptoms. Amyloid beta-peptide 1-42 (A beta (1-42)) is considered one of the key pathological AD biomarkers that is present in different biological fluids. However, A beta (1-42) detection still relies on colorimetric and enzyme-linked immunoassays as the gold standard characterized by low accuracy or high costs, respectively. In this context, optical detection techniques based on surface-enhanced Raman spectroscopy (SERS) through advanced nanoconstructs are promising alternatives for the development of novel rapid and low-cost methods for the targeting of A beta pathological biomarkers in fluids. Here, a multilayered nanoprobe constituted by bioorthogonal Raman reporters (RRs) embedded within two layers of gold nanoparticles (Au@RRs@AuNPs) has been developed and successfully validated for specific detection of A beta (1-42) in the human cerebrospinal fluid (CSF) with sensitivity down to pg/mL. The smart double-layer configuration enables us to exploit the outer gold NP surfaces for selective absorption of targeted peptide whose concentration controls the aggregation behavior of Au@RRs@AuNPs, proportionally reflected in Raman intensity changes, providing high specificity and sensitivity and representing a significant step ahead of the state of the art on SERS for clinical analyses.

Journal/Review: ACS SENSORS

Volume: 8 (10)      Pages from: 3693  to: 3700

More Information: This work was supported by DoptoScreen project (Fondo di Beneficenza Intesa San Paolo 2019, B/2019/0289) and RISE project. The authors also wish to acknowledge Fulvio Ratto, Sonia Centi, and Roberto Pini (Institute of Applied Physics ’N. Carrara’, CNR-Florence, Italy) for their assistance in the experiments. The authors would like also to t hank the Centre for Electron Microscopies (Ce.ME) and the Centro di competenza-RISE funded by FAS Regione Toscana.
KeyWords: multilayered nanoparticles; SERS-based sensors; bioorthogonal Raman; cerebrospinal fluid; A beta(1-42) peptides; neurodegenerative biomarker
DOI: 10.1021/acssensors.3c00225

Citations: 7
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