Hypoxia-Activated Fluorescent Probe Based on Self-Immolative Block Copolymer.

This work reports a hypoxia-activated fluorescent probe for tumor imaging by using self-immolative block copolymer with azobenzene linkage. The water-soluble polymer composed of self-immolative building blocks shows no obvious fluorescence. Under the hypoxic microenvironment of tumor cells, the azobenzene is reduced by the overexpressed azoreductase, which will trigger a domino-like disassembly of the self-immolative polymer. The released building blocks from the self-immolative polymer emit strong fluorescence, which shows the potential application in tumor imaging.

Hypoxia-Triggered In Situ Self-Assembly of a Charge Switchable Azo Polymer with AIEgens for Tumor Imaging.

In recent years, stimuli-responsive in situ self-assembly fluorescent probes for tumor imaging, which leverage the advantage of efficient penetrability and satisfactory accumulation, have attracted much attention. In this work, we rationally integrate charge switchable azobenzene moiety and long wavelength aggregation-induced emission fluorogens (AIEgens) into one water-soluble polymer to construct the hypoxia-triggered in situ self-assembly fluorescent probe for tumor imaging. Due to the good water solubility and the quenching effect of azobenzene moiety, the AIEgens containing polymer showed no significant fluorescence. Under a tumor hypoxic environment, the enzymatic reduction of azobenzene triggered cationic quaternary ammonium converting into anionic carboxylate. Then self-assembly nanoparticles were obtained, driven by the electrostatic interaction between negatively charged carboxylate ion and positively charged AIEgens, which emitted a strong orange-red fluorescence.

In situ construction of a self-assembled AIE probe for tumor hypoxia imaging.

This communication reported a hypoxia-responsive fluorescent probe based on the in situ concept, which combines a water-soluble azobenzene containing copolymer with a carbamate linkage and an anionic water-soluble aggregation-induced emission fluorogen (AIEgen) tetraphenylethene (TPE). The water-soluble copolymer can be transformed into a protonated primary amine containing polymer by the reduction of the azo bond and through a 1,6-self elimination cascade reaction under hypoxic conditions. The transition of anionic TPE from the molecular dispersed state to the aggregation state induced by self-assembly with the cationic polymer would lead to an obvious increase in fluorescence according to the AIE characteristics.

Strategies for Tumor Hypoxia Imaging Based on Aggregation-Induced Emission Fluorogens.

Hypoxia, as a crucial characteristic of cancer, has become an extremely significant direction for researchers to construct fluorescent probes for early diagnosis of tumors. Aggregation-induced emission fluorogens (AIEgens) possess many superior properties to those of conventional fluorophores due to aggregation-induced emission (AIE) features, such as a linear concentration-dependent increase in brightness, remarkable resistance to photobleaching, and the long-term tracking and imaging of cells. Constructing hypoxic response AIEgen-based probes will be very useful for the early diagnosis of tumors. Herein, several hypoxia-responsive probes based on AIEgens reported in the last three years are reported; these examples may lead to the construction of hypoxia-responsive AIE probes used for tumor hypoxia imaging in the future. In addition, typical, conventional hypoxia-responsive bioprobes are presented to further understand hypoxia-responsive fluorescent probes based on AIEgens.