Hemicyanine-Based Wash-Free Near-Infrared Fluorescent Probe for Imaging Amyloid-β Aggregates in Alzheimer’s Disease
- 1Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China
Abstract
As a key biomarker of Alzheimer’s disease (AD), amyloid-β (Aβ) is frequently employed for the diagnosis of AD. Near-infrared fluorescence (NIRF) imaging is a non-invasive, low-cost route for visualizing Aβ in vivo. However, most existing Aβ NIRF probes require tedious washing steps, show modest fluorescence turn-on (<50-fold), and stain normal tissue non-specifically. In this work, by fine-tuning the amphiphilicity of a hemicyanine scaffold to place its log P within the appropriate range, we identified P3 as a wash-free NIRF probe for Aβ aggregates. P3 bound Aβ aggregates with high affinity. In vivo, P3 distinguished AD mice from wild-type mice with a 4.8-fold signal ratio, together with adequate brain uptake (1.5 ± 0.1 ID/g at 20 min) and rapid clearance. Unlike Thioflavin T, which indiscriminately labels Aβ aggregates and normal neurons, P3 specifically labeled Aβ aggregates with negligible background, which enabled wash-free imaging with a signal-to-noise ratio of 80 ± 4. This work provides a wash-free, high-affinity NIRF probe for Aβ imaging.
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BibTeX
@article{zhao2026hemicyaninebased,
title = {{Hemicyanine-Based Wash-Free Near-Infrared Fluorescent Probe for Imaging Amyloid-β Aggregates in Alzheimer’s Disease}},
author = {Xueqi Zhao and Rundong Liang and Yao Li and Jiawei Yan and Jing Zhang and Zheng Su and Yang Liu and Huali Yang and Maosheng Cheng},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203624},
url = {https://www.mdpi.com/1420-3049/31/20/3624},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hemicyanine-Based Wash-Free Near-Infrared Fluorescent Probe for Imaging Amyloid-β Aggregates in Alzheimer’s Disease
AU - Xueqi Zhao
AU - Rundong Liang
AU - Yao Li
AU - Jiawei Yan
AU - Jing Zhang
AU - Zheng Su
AU - Yang Liu
AU - Huali Yang
AU - Maosheng Cheng
PY - 2026
DA - 2026/10/11
JO - Molecules
DO - 10.3390/molecules31203624
UR - https://www.mdpi.com/1420-3049/31/20/3624
AB - As a key biomarker of Alzheimer’s disease (AD), amyloid-β (Aβ) is frequently employed for the diagnosis of AD. Near-infrared fluorescence (NIRF) imaging is a non-invasive, low-cost route for visualizing Aβ in vivo. However, most existing Aβ NIRF probes require tedious washing steps, show modest fluorescence turn-on (<50-fold), and stain normal tissue non-specifically. In this work, by fine-tuning the amphiphilicity of a hemicyanine scaffold to place its log P within the appropriate range, we identified P3 as a wash-free NIRF probe for Aβ aggregates. P3 bound Aβ aggregates with high affinity. In vivo, P3 distinguished AD mice from wild-type mice with a 4.8-fold signal ratio, together with adequate brain uptake (1.5 ± 0.1 ID/g at 20 min) and rapid clearance. Unlike Thioflavin T, which indiscriminately labels Aβ aggregates and normal neurons, P3 specifically labeled Aβ aggregates with negligible background, which enabled wash-free imaging with a signal-to-noise ratio of 80 ± 4. This work provides a wash-free, high-affinity NIRF probe for Aβ imaging.
SN - 1420-3049
ER -