Phenothiazine-based theranostic compounds for in vivo near-infared fluorescence imaging of β-amyloid plaques and inhibition of Aβ aggregation

Li, Yong Liang; Cai, Jing; Yan, Longjia; Zhang, Wanzheng; Li, Li; Du, Zhiyun; Fang, Yan; Dong, Chunhui; Meunier, Bernard; Chen, Huixiong

doi:10.1016/j.dyepig.2019.107744

Cited by 10 publications

(17 citation statements)

References 33 publications

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“…In 2019, Chen et al designed and synthesized a series of poly(ethylene glycol)-modified probes with methoxyl terminals. After intravenous injection of probe 4, 12-month-old APP/PS1 mice exhibited a higher relative signal than the control mice over the same period of time, and ex vivo fluorescence observations confirmed the existence of Aβ plaques (Figure c) . In addition, 5a was designed by increasing the conjugate chain length to further improve the emission wavelength .…”

Section: Nirf Probes For β-Amyloid Detectionmentioning

confidence: 94%

“…After intravenous injection of probe 4, 12-monthold APP/PS1 mice exhibited a higher relative signal than the control mice over the same period of time, and ex vivo fluorescence observations confirmed the existence of Aβ plaques (Figure 13c). 50 In addition, 5a was designed by increasing the conjugate chain length to further improve the emission wavelength. 12 Despite emission maximum wavelength at 700 nm, its binding affinity to Aβ plaques declines considerably (K d = 10.2 nM).…”

Section: Nirf Probes For β-Amyloid Detectionmentioning

confidence: 99%

Section: Nirf Probes For β-Amyloid Detectionmentioning

confidence: 99%

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Development of Near-Infrared Fluorescent Probes for Use in Alzheimer’s Disease Diagnosis

Yang

Zeng

et al. 2019

Bioconjugate Chem.

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Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder. Currently, there are no available treatments that can effectively stop or reverse the progression of the disease, and existing therapeutics can only alleviate the symptoms. Thus, it remains urgent to develop effective early-stage AD diagnostic methods. In recent years, the search for near-infrared fluorescent (NIRF) probes of AD hallmarks has become a promising research field. In this Review, we will focus on small-molecule NIRF probes used to detect β-amyloid, tau proteins, and reactive oxygen species in vivo during the past 4 years. We believe that some new directions we raise herein will benefit the future development of NIRF probes in the field of AD research.

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Section: Nirf Probes For β-Amyloid Detectionmentioning

confidence: 94%

Section: Nirf Probes For β-Amyloid Detectionmentioning

confidence: 99%

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Development of Near-Infrared Fluorescent Probes for Use in Alzheimer’s Disease Diagnosis

Yang

Zeng

et al. 2019

Bioconjugate Chem.

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“…In fact, many drug candidates intervene at an advanced stage of AD when insoluble Aβ plaques have already formed and caused irreversible damage to the neurons. 26 Thus, detecting and monitoring Aβ levels at an early stage is considered the most effective strategy to controlling and delaying the progress of AD. The past decade has witnessed impressive advances in the design of Aβ probes.…”

Section: ■ Introductionmentioning

confidence: 99%

Design of Self-Assembled Nanoparticles as a Potent Inhibitor and Fluorescent Probe for β-Amyloid Fibrillization

Wang,

Liu,

Dong

et al. 2023

Langmuir

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Alzheimer's disease (AD) remains incurable due to its complex pathogenesis. The deposition of β-amyloid (Aβ) in the brain appears much earlier than any clinical symptoms and plays an essential role in the occurrence and development of AD neuropathology, which implies the importance of early theranostics. Herein, we designed a self-assembled bifunctional nanoparticle (LC8-pCG-fLC8) for Aβ fluorescent diagnosis and inhibition. The nanoparticle was synthesized by click chemistry from Aβtargeting peptide Ac-LVFFARKC-NH 2 (LC8) and an Aβ fluorescent probe f with the zwitterionic copolymer poly(carboxybetaine methacrylate-glycidyl methacrylate) (p(CBMA-GMA), pCG). Owing to the high reactivity of epoxy groups, the peptide concentration of LC8-pCG-fLC8 nanoparticles reached about 4 times higher than that of the existing inhibitor LVFFARK@ poly(carboxybetaine) (LK7@pCB). LC8-pCG-fLC8 exhibited remarkable inhibitory capability (suppression efficiency of 83.0% at 20 μM), altered the aggregation pathway of Aβ, and increased the survival rate of amyloid-induced cultured cells from 76.5% to 98.0% at 20 μM. Notably, LC8-pCG-fLC8 possessed excellent binding affinity, good biostability, and high fluorescence responsivity to β-sheet-rich Aβ oligomers and fibrils, which could be used for the early diagnosis of Aβ aggregation. More importantly, in vivo tests using transgenic C. elegans CL2006 stain showed that LC8-pCG-fLC8 could specifically image Aβ plaques, prolong the lifespan (from 13 to 17 days), and attenuate the AD-like symptoms (reducing paralysis and Aβ deposition). Therefore, self-assembled nanoparticles hold great potential in AD theranostics.

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“…However, fluorescence imaging of in vivo and post-mortem brain tissue can be impeded by spatially heterogeneous background autofluorescence originating from multiple sources including emission of unbound or off-target bound dye and endogenous fluorophores, which is exacerbated in aged subjects . A variety of approaches have been reported in the literature to address this issue, including histochemical quenching, − photobleaching, background subtraction, , near-infrared dyes, ,− and fluorescence lifetime imaging microscopy (FLIM) . FLIM is highly suited to the study of amyloid and can be used to exploit the sensitive response of the excited-state dynamics of amyloid probes to changes in their local environment.…”

Section: Introductionmentioning

confidence: 99%

A Comparative Study of High-Contrast Fluorescence Lifetime Probes for Imaging Amyloid in Tissue

et al. 2021

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Optical imaging of protein aggregates in living and post-mortem tissue can often be impeded by unwanted fluorescence, prompting the need for novel methods to extract meaningful signal in complex biological environments. Historically, benzothiazolium derivatives, prominently Thioflavin T, have been the state-of-the-art fluorescent probes for amyloid aggregates, but their optical, structural, and binding properties typically limit them to in vitro applications. This study compares the use of novel uncharged derivative, PAP_1, with parent Thioflavin T as a fluorescence lifetime imaging probe. This is applied specifically to imaging recombinant α-synuclein aggregates doped into brain tissue. Despite the 100-fold lower brightness of PAP_1 compared to that of Thioflavin T, PAP_1 binds to α-synuclein aggregates with an affinity several orders of magnitude greater than Thioflavin T; thus, we observe a specific decrease in the fluorescence lifetime of PAP_1 bound to α-synuclein aggregates, resulting in a separation of >1.4 standard deviations between PAP_1-stained brain tissue background and α-synuclein aggregates that is not observed with Thioflavin T. This enables contrast between highly fluorescent background tissue and amyloid fibrils that is attributed to the greater affinity of PAP_1 for α-synuclein aggregates, avoiding the substantial off-target staining observed with Thioflavin T.

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Phenothiazine-based theranostic compounds for in vivo near-infared fluorescence imaging of β-amyloid plaques and inhibition of Aβ aggregation

Cited by 10 publications

References 33 publications

Development of Near-Infrared Fluorescent Probes for Use in Alzheimer’s Disease Diagnosis

Development of Near-Infrared Fluorescent Probes for Use in Alzheimer’s Disease Diagnosis

Design of Self-Assembled Nanoparticles as a Potent Inhibitor and Fluorescent Probe for β-Amyloid Fibrillization

A Comparative Study of High-Contrast Fluorescence Lifetime Probes for Imaging Amyloid in Tissue

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