Image-guided photodynamic therapy (PDT) can realize highly precise and effective therapy due to the integration of imaging and therapy, and put forward high requirement for photosensitizers. However, the PDT modality...
Autophagy is crucial in the physical development and pathogenesis of disease. Monitoring autophagy is still limited by no real-time and poor specificity. Herein, the authors report studies of Atg4B enzyme as a biomarker for autophagy and the development of an Atg4B-responsive aggregation-induced emission (AIE) probe, termed QM-GFTN. Particularly, the incorporated peptide unit of GFTN endows good dispersion, but the state can be reversed when the hydrophilic peptide is cleaved by the Atg4B, thus realizing a light-up fluorescence with high signal/noise (S/N) ratio. The probe exhibits excellent selectivity to Atg4B, and can respond to its activity in solution and living cells, thus efficiently distinguishing autophagy-active from autophagy-inactive states, greatly shortening the detection time comparing to the traditional methods. The fluorescence imaging of cells and autophagy-inhibitor studies indicate that QM-GFTN is specifically cleaved by Atg4B, and rules out the possibility of its self-aggregation. By grafting Atg4B-cleavable peptide to AIE fluorophore, the peptide-based probe can carry out real-time visualization of Atg4B activity with guaranteeing high specificity, serving as a great breakthrough to the detection of autophagy process in various autophagic cells, animal tissues, and even human pathological tissues.
Aggregation induced emission (AIE) photosensitizers have attracted great attention due to their good performance in photodynamic therapy (PDT). However, the therapeutic effect of AIE photosensitizer is often highly dependent on the biological microenvironment because it is difficult to produce type I and type II reactive oxygen species (ROS) simultaneously. Herein, an electron‐rich anion‐π+ AIEgen Pys‐QM‐TT is reported, which is capable of highly generating type I and type II ROS and realizing near‐infrared fluorescence imaging synchronously. In the rational design of AIE photosensitizer, the strong electron‐donating triphenylamine unit, π‐bridge thiophene and electron‐withdrawing pyridinium salt unit can enhance the D–π–A behavior, thereby improving the intramolecular charge transfer effect and extending the wavelength. Meanwhile, the powerful D–π–A effect is supposed to reduce ∆ES‐T and promote the intersystem crossing processes, thus increasing the generation of ROS. In addition, the negatively charged anion in pyridinium salt group provides an electron‐rich environment for the excited photosensitizer, so as to promote electron transfer to generate type I ROS. Therefore, Pys‐QM‐TT can not only generate type I and type II ROS simultaneously with weak environmental dependence, but also effectively inhibit bacterial infections and ablate tumor tissue by promoting tumor cell apoptosis, inhibiting tumor cell proliferation and anti‐angiogenesis.
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