Search

Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health.

Nuclei and mitochondria are the only cellular organelles containing genes, which are specific targets for efficient cancer therapy. So far, several photosensitizers have been reported for mitochondria targeting, and another few have been reported for nuclei targeting. However, none have been reported for photosensitization in both mitochondria and nucleus, especially in cascade mode, which can significantly reduce the photosensitizers needed for maximal treatment effect. Herein, a light-driven, mitochondria-to-nucleus cascade dual organelle cancer cell ablation strategy is reported. A functionalized iridium complex, named BT-Ir, is designed as a photosensitizer, which targets mitochondria first for photosensitization and subsequently is translocated to a cell nucleus for continuous photodynamic cancer cell ablation. This strategy opens new opportunities for efficient photodynamic therapy.

The integration of pyroptosis and ferroptosis hybrid cell death induction to augment immune activation represents a promising avenue for anti‐tumor treatment, but there is a lack of research. Herein, we developed two iridium (III)‐triphenylamine photosensitizers, IrC and IrF, with the capacity to disrupt redox balance and induce photo‐driven cascade damage to DNA and Kelch‐like ECH‐associated protein 1 (KEAP1). The activation of the absent in melanoma 2 (AIM2)‐related cytoplasmic nucleic acid‐sensing pathway, triggered by damaged DNA, leads to the induction of gasdermin D (GSDMD)‐mediated pyroptosis. Simultaneously, iron homeostasis, regulated by the KEAP1/nuclear factor erythroid 2‐related factor 2 (NRF2)/heme oxygenase 1 (HO‐1) pathway, serves as a pivotal bridge, facilitating not only the induction of gasdermin E (GSDME)‐mediated non‐canonical pyroptosis, but also ferroptosis in synergy with glutathione peroxidase 4 (GPX4) depletion. The collaborative action of pyroptosis and ferroptosis generates a synergistic effect that elicits immunogenic cell death, stimulates a robust immune response and effectively inhibits tumor growth in vivo. Our work introduces the first metal‐based small molecule dual‐inducers of pyroptosis and ferroptosis for potent cancer immunotherapy, and highlights the significance of iron homeostasis as a vital hub connecting synergistic effects of pyroptosis and ferroptosis. [ABSTRACT FROM AUTHOR]

With the development of metalloimmunology, the potential of platinum drugs in cancer immunotherapy has attracted extensive attention. Although immunochemotherapy combining PD‐1/PD−L1 antibodies with platinum drugs has achieved great success in the clinic, combination therapy commonly brings new problems. Herein, we have developed a platinum‐metformin conjugate as a promising alternative to antibody‐based PD−L1 inhibitors, not only disrupting PD‐1/PD−L1 axis on cell surface but also down‐regulating the total PD−L1 levels in non‐small cell lung cancer (NSCLC) cells comprehensively, thus achieving highly efficient immunochemotherapy by a single small molecule. Mechanism studies demonstrate that Pt‐metformin conjugate can selectively accumulate in lysosomes, promote lysosomal‐dependent PD−L1 degradation via the AMPK‐TFEB pathway, and modulate the upstream regulatory proteins related to PD−L1 expression (e.g. HIF‐1α and NF‐κB), eventually decreasing the total abundance of PD−L1 in NSCLC, overcoming tumor hypoxia, and activating anti‐tumor immunity in vivo. This work suggests an AMPK‐mediated lysosomal degradation pathway of PD−L1 for the first time and provides a unique design perspective for the development of novel platinum drugs for immunochemotherapy. [ABSTRACT FROM AUTHOR]

Ruthenium polypyridyl complexes are promising anticancer candidates, while their cellular targets have rarely been identified, which limits their clinical application. Herein, we design a series of Ru(II) polypyridyl complexes containing bioactive β-carboline derivatives as ligands for anticancer evaluation, among which Ru5 shows suitable lipophilicity, high aqueous solubility, relatively high anticancer activity and cancer cell selectivity. The subsequent utilization of a photo-clickable probe, Ru5a , serves to validate the significance of ATP synthase as a crucial target for Ru5 through photoaffinity-based protein profiling. Ru5 accumulates in mitochondria, impairs mitochondrial functions and induces mitophagy and ferroptosis. Combined analysis of mitochondrial proteomics and RNA-sequencing shows that Ru5 significantly downregulates the expression of the chloride channel protein, and influences genes related to ferroptosis and epithelial-to-mesenchymal transition. Finally, we prove that Ru5 exhibits higher anticancer efficacy than cisplatin in vivo. We firstly identify the molecular targets of ruthenium polypyridyl complexes using a photo-click proteomic method coupled with a multiomics approach, which provides an innovative strategy to elucidate the anticancer mechanisms of metallo-anticancer candidates. [ABSTRACT FROM AUTHOR]