A selective and sensitive near-infrared fluorescent probe for acetylcholinesterase imaging

Abstract

Two near infra-red (NIR) fluorescent probes HupNIR1 and HupNIR2 based on the huprine scaffold and cyanine 5.0 dye have been synthesised and evaluated in situ for the detection of acetylcholinesterases in different tissues. As anticipated by the initial properties of huprine, both probes displayed a high affinity and selectivity for AChE toward BChE, with IC50 values in the nanomolar range and without any non-specific binding in the tissues. HupNIR2 appears the best probe for AChE with a great selectivity and sensitivity for AChE even in the brain region displaying a low AChE concentration as striatum. Moreover, the binding of HupNIR2 is affected when AChE is inhibited with toxic molecules such as organophosphates. This work provides a new tool to visualize active AChE in biological applications.

Cyanine Conjugate‐Based Biomedical Imaging Probes

“…[47] OTL78 (35) and YC-27 (36) are two representative conjugates based on DUPA and KuE, respectively. Other inhibitors, including huprine and SeISA, were also reported to conjugate with cyanine fluorophores for targeted imaging of acetylcholinesterase in neuromuscular junction (37), [48] and histone deacetylase 6 in breast tumor xenograft (38). [49] Based on understanding of the mechanism of action, inhibitors can be modified to acquire desirable targeting profiles.…”

“…Based on similar structure-switching mechanism, some self-fluorescent nanomaterials such as silicon nanodots (SiNDs), [65] oxidized mesoporous carbon nanospheres, [66] carbon nanoparticles, [67] and reduced graphene oxide, [68] have been integrated into cyanine-aptamer conjugates, either covalently or noncovalently. One representative activatable probe (48) was constructed by coupling Cy5-labeled S2.2 aptamer with SiND via a bifunctional crosslinker (Sulfo-SMCC) for turn-on detection of mucin 1 (MUC1).…”

Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes

“…Fluorescent probes are particularly useful here, due to the high sensitivity of fluorescence techniques and the potential for visualisation through various fluorescence microscopy techniques. Numerous AChE-specific fluorescent inhibitors have been reported, some of which are irreversible and some of which are competitive [8][9][10][11] . A tacrine-based fluorescent inhibitor with high affinity towards both AChE and BChE has been described, and this was shown to stain Ab plaques when used as a probe for histochemical staining of brain tissue 12 .…”

Targeted Methotrexate Prodrug Conjugated With Heptamethine Cyanine Dye Improving Chemotherapy and Monitoring Itself Activating by Dual-Modal Imaging

“…However, it is still challenging to design SCTPs which have an excellent ability of targeting tumor, monitor the location and activation of prodrug, improve the therapeutic effect simultaneously. Nowadays, heptamethine cyanine dyes have been widely used for tracking prodrug activation due to their excellent optical properties in the near-infrared (Wu et al, 2014(Wu et al, , 2015aChao et al, 2016;Sun et al, 2016;Ye et al, 2016;Atchison et al, 2017). What's more, some of them present the excellent tageting ability to tumor due to overexpression of certain types of organic anion transport peptide in cancer cell (Wu et al, 2015b;Shi et al, 2016;Guan et al, 2017;Meng et al, 2017).…”