Making Aggregation-Induced Emission Luminogen More Valuable by Gold: Enhancing Anticancer Efficacy by Suppressing Thioredoxin Reductase Activity

Abstract

Gold complexes have been recognized as potential anticancer agents against various kinds of diseases due to their inherent suppressions of antioxidant thioredoxin reductase (TrxR) activity. Herein, a powerful aggregationinduced emission luminogen (AIEgen), TBP-Au, was designed and synthesized by integrating an anticancer Au(I) moiety with an AIE-active photosensitizer (TBP), in which both the production and consumption routes of reactive oxygen species (ROS) were elaborately considered simultaneously to boost the anticancer efficacy. It has been demonstrated that TBP-Au could realize superior two-photon fluorescence imaging in tumor tissues with high resolution and deep penetration as well as long-term imaging in live animals due to its AIE property. In addition, the introduction of a special Au(I) moiety could tune the organelle specificity and efficiently facilitate the ROS-determined photodynamic therapy (PDT). More impressively, TBP-Au could efficiently eliminate cancer cells under light irradiation through the preconceived synergetic approaches from the PDT and the effective suppression of TrxR, demonstrating that TBP-Au holds great potential for precise cancer theranostics.

The fast-growing field of photo-driven theranostics based on aggregation-induced emission

“…9d). 213 In addition to the efficient ROS generation capacity of the TBP ligand, the superefficiency of the anticancer therapy could also be synergetically attributed to the Au(I)-caused effective suppression of antioxidant TrxR, which was able to retard the unexpected ROS consumption. Taking both the ROS generation and consumption pathways into consideration, TBP-Au could smoothly execute an impressive ''1 + 1 4 2'' photodynamic elimination of cancer cells.…”

Recent Advances in the Fluorescent Probes for Flavinase Activity: Design and Applications

“…To inhibit the activity of TrxR in cancer cells with appropriate inhibitors can stimulate the production of reactive oxygen species (ROS), further breaking cell redox homeostasis and eventually inducing apoptosis of cancer cells. Based on this principle, Zou and coworkers designed and synthesized a photosensitive probe 29 (Figure 17), [49] a gold complex with inhibitory effect on TrxR activity. It achieved ultraefficient cancer treatment through the synergistic effect of photodynamic therapy (PDT) and TrxR system activity inhibition.…”

Metal‐Based Aggregation‐Induced Emission Theranostic Systems

“…To perform more precise anticancer theranostics, Zhang et al. further developed an NIR‐emissive AIE‐active gold complex named TBP‐Au through the combination of the AIE ligand (TBP) into the Au(I) complex (Figure 1E) [46] . The interaction between TBP and Au not only generated an NIR‐emissive Au(I) complex, but also gave TBP strong capability in generating ROS.…”