Luminescent lanthanide complexes for reactive oxygen species biosensing and possible application in Alzheimer’s diseases

Abstract

Histopathological hallmarks of Alzheimer's disease (AD) are intracellular neurofibrillary tangles and extracellular formation of senile plaques composed of the aggregated amyloid-beta peptide along with metal ions (copper, iron or zinc). In addition, oxidative stress is considered as an important factor in the etiology of AD and a multitude of metalloproteins and transporters is affected, leading to metal ion misregulation. Redox-active metal ions (e.g., copper) can catalyze the production of reactive oxygen species (ROS) in the presence of molecular oxygen and a reductant such as ascorbate. The ROS thus produced, in particular the hydroxyl radical which is the most reactive one, may contribute to oxidative stress conditions. Thus, detecting ROS in vivo or in biological models of AD is of interest for better understanding AD etiology. The use of biocompatible and highly specific and sensitive probes is needed for such a purpose, since ROS are transient species whose steady-state concentrations are very low. Luminescent lanthanide complexes are sensitive probes that can meet these criteria. The present review focuses on the recent advances in the use of luminescent lanthanide complexes for ROS biosensing. It shows why the Abbreviations 2-HO-E + , 2-hydroxyethidium; 4-HNE, 4-hydroxynonenal; ABC transporters, ATP-binding cassette transporters; AD, Alzheimer's disease; AMTTA, 4'-(p-aminophenoxy)methylene-2,2':6',2''-terpyridine-6,6''-diyl]bis(methylenenitrilo)tetrakis(acetate); APF, 3'-(p-AminoPhenyl) Fluorescein; ATTA, 4 0 -(9-anthryl)-2,2 0 ∶6 0 ,2″-terpyridine-6,6″-diyl]bis(methylenenitrilo) tetrakis (acetate); Aβ, amyloid-beta peptide; BBB, blood-brain barrier; BET, back energy transfer;

Regenerative Activities of ROS-Modulating Trace Metals in Subcutaneously Implanted Biodegradable Cryogel

“…Earlier, the macroporous structure of cryogels allowed us to monitor bulk affinity interactions of the materials with fluorescently labeled peptide ligands [ 34 ]. Similarly, the interaction of H 2 O 2 with TM-doped cryogels was assessed using an ROS-sensitive DCFDA probe, considering H 2 O 2 as both an extracellular and intracellular precursor of ROS generated in Fenton-like reactions [ 29 , 51 ]. The hydroxyl radical is particularly recognized as a secondary messenger involved in cell redox regulation via oxidizing thiols and activating transcriptional factors such as HIF-1α [ 52 ].…”

Redox signaling and metabolism in Alzheimer's disease

“…•− , • OH, 1 O 2 , and H 2 O 2 in a µM to nM range (Galaup et al, 2021). Disadvantages of probes for the in vivo detection of redox reactive compounds may include artifactual amplification of the intensity by the formation of intermediate radicals, light sensitivity leading to artifactual H 2 O 2 generation, reaction with other reactive species, and interference/dependency of the reaction on enzymatic activity (Kalyanaraman et al, 2012).…”

“…Numerous fluorescent probes for detection of varying redox active species (ROS/RNS/RSS) in vivo/in cellulo are summarized in (Lü, 2017 ) and (Wu et al, 2019 ). Luminescent lanthanide complexes selectively detect i.e., O 2 •− , • OH, 1 O 2 , and H 2 O 2 in a μM to nM range (Galaup et al, 2021 ). Disadvantages of probes for the in vivo detection of redox reactive compounds may include artifactual amplification of the intensity by the formation of intermediate radicals, light sensitivity leading to artifactual H 2 O 2 generation, reaction with other reactive species, and interference/dependency of the reaction on enzymatic activity (Kalyanaraman et al, 2012 ).…”

Biomedical Applications of Lanthanide Nanomaterials, for Imaging, Sensing and Therapy

“…By irradiating the NIR light to the upconversion nanoparticle, the NIR light can be transferred to UV light, further activating the K indicator to detect the intracellular K + level [61]. Chantal Galaup et al evaluated a possibility of luminescent lanthanide material that could detect ROS in the context of Alzheimer's disease [62]. Cyrille Charpentier et al designed a particular ligand that could boost the brightness of the terbium nanoparticles and link the nanoparticle to different biological molecules to form specific biosensors to detect biotinylated dyes or even epidermal growth factor receptors (EGFR) [63].…”