A New Strategy toward “Simple” Water‐Soluble AIE Probes for Hypoxia Detection

Abstract

Hypoxia-responsive fluorescent probes have emerged as a novel scaffold for tumor diagnosis. However, dilemma often exists between simple synthesis and high water solubility in traditional probes. Owing to the intrinsic property of N-oxides, herein, a new strategy is proposed to design and synthesize probes for in vitro hypoxia imaging. Equipped with tetraphenylethene (TPE), the N-oxides exhibit aggregation-induced emission characteristics and emit no light in aqueous solutions. Interestingly, the N-oxides can be reduced by ferrous ions in different rates. The aggregation of the resulting hydrophobic TPE residues restricts the intramolecular motions of the molecules, which "turns-on" their fluorescence. The NO covalent bond of one molecule can be specifically cleaved by cellular reductase overexpressed under hypoxic conditions, and thus turn-on hypoxia imaging in vitro is achieved. The new strategy to design hypoxia imaging probes is extremely valuable and has great potential for application in tumor diagnosis.

Measurement of Solubilization Location in Micelles Using Anchored Aggregation‐Induced Emission Donors

“…The emission peak located at about 485 nm, which agreed well with the emission wavelength of TPE aggregates. [15] Interestingly, the relationship between the emission intensity and the concentration (Figure 2 d) was similar to that between the conductivity and the concentration (Figure 2 a). The increasing rate of fluorescence intensity of TPE-C 10 TEAB varied when the TPE-C 10 TEAB concentrations were below and above about 42 mm (ca.…”

Activatable NIR‐II Plasmonic Nanotheranostics for Efficient Photoacoustic Imaging and Photothermal Cancer Therapy

“…[ 22,24 ] The other is that most reported theranostic nanoagents are “always‐on” regardless of whether they are in tumor tissue or normal tissue, which may lead to difficulties in diagnosis including serious side effects on normal tissues. [ 20,25–30 ] In contrast to normal tissues, the tumor microenvironment (TME) has unique characteristics including enhanced permeability and retention effects, mild acidic nature, disordered redox potentials, and hypoxia, as well as the overexpressed biosynthetic intermediates. Developing TME‐triggered theranostic nanoagents could offer promising perspectives to address the above limitations achieving “off”‐to‐“on” switching tumor‐specific detection and therapy.…”

Strategies for Tumor Hypoxia Imaging Based on Aggregation‐Induced Emission Fluorogens

“…Several conventional fluorescent probes based on N + −O − have been reported in recent years . Hypoxia‐responsive N + −O − ‐containing AIE fluorescent probes were reported by Tang and co‐workers recently, for the first time (Figure ) . N + −O − ‐based TPE derivatives with different substituents (TPE‐2M N‐oxide, TPE‐2E N‐oxide, and TPE‐2M2F N‐oxide) were synthesized through the McMurry cross‐coupling reaction, followed by a subsequent oxidation process.…”

“…[55,56] Hypoxia-responsiveN + ÀO À -containing AIE fluorescent probes werer eported by Tang and co-workersr ecently,f or the first time (Figure 7). [57] N + ÀO Àbased TPE derivativesw ith different substituents (TPE-2MNoxide, TPE-2E N-oxide, and TPE-2M2F N-oxide) were synthesized through the McMurryc ross-couplingr eaction, followed by as ubsequent oxidation process. TPE-2M N-oxide, TPE-2E Noxide, andT PE-2M2F N-oxide can disperse well in aqueous medium, leading to negligible fluorescencei nw ater.I nv itro imagingw as carriedo ut to examine the hypoxia-responsive property of TPE-2M N-oxide towards reductase overexpressed in the hypoxicm icroenvironment.…”