Near-Infrared Photooxygenation Theranostics Used for the Specific Mapping and Modulating of Amyloid-β Aggregation

Abstract

The photooxygenation of amyloid-β (Aβ) protein is considered a promising strategy against Alzheimer's disease (AD). The inhibition of Aβ aggregation or depolymerization of Aβ aggregates can effectively alleviate and improve the condition of AD. Herein, we report a series of "off−on" near-infrared quinolinium photosensitizers (QM20−QM22) based on D-π-A structures using a target-sensing catalyst activation (TaSCAc) strategy. They exhibit turn-on fluorescence when bonded to Aβ aggregates and generate singlet oxygen to achieve the specific imaging and photooxygenation of Aβ aggregates, leading to attenuated Aβ aggregates, enhancing their clearance through the microglial lysosomal pathway, decreasing their neurotoxicity. This study will shed light on the development of the photooxygenation of misfolded proteins for the treatment of neurodegenerative diseases.

Small Molecular Fluorescent Probes for Alzheimer's Disease Associated Active Species

“…Yan and colleagues reported three near-infrared (NIR) quinolinium photosensitizers 1 a-1 c (Figure 2) based on donorπ-acceptor (D-π-A) structures and the target-sensing catalyst activation strategy for turn-on response and depolymerization of Aβ aggregates. [41] These compounds were composed of quinolinium (electron acceptor), dimethylaniline group (electron donor) and different length of the vinyl group (π-bridge). In the probe, the N,N-dimethylamino moiety acted as not only a donor but also the Aβ aggregates recognition moiety.…”

Design of aggregation-induced emission-active fluorogen-based nanoparticles for imaging and scavenging Alzheimer's β-amyloid by photo-oxygenation

“…However, to the best of our knowledge, the multiple ROS generation capability of photo-oxidants for AD treatment is barely reported in the literature (Table S1, ESI †). 13,48,50,52,53 Because T-LD NPs retained the photophysical properties of TPMD (including absorption spectra, fluorescence spectra and ROS generation capability), the multiple ROS generation capability of T-LD NPs should originate from the TPMD cores in the T-LD NPs. 42 The superior ROS generation capability of NPs implied the great potential for the following Ab photo-oxygenation study.…”

“…As reported previously, diverse Ab scavengers, including small molecules, 12,13 proteins, 14 nanomaterials, 15,16 and peptides, 17,18 have been designed to modulate the on-pathway fibrillization. When compared with others, the scavengers based on nanomaterials display outstanding advantages, such as easy functionalization, desirable biodegradability, and high biocompatibility.…”

Recent progress of small-molecule-based theranostic agents in Alzheimer's disease

“…4). 46 They were composed of a quinolinium scaffold as the electron acceptor, a dimethylaniline group as the electron donor, and vinyl groups with different length as π-bridges. The authors believed that the binding of the photosensitizers with Aβ aggregates would turn on their NIR fluorescence and promote the production of singlet oxygen through the inhibition of intramolecular rotation of the structure and twisted-intramolecular charge transfer (TICT) process.…”