Search

We herein present an approach of photo‐induced disproportionation for preparation of Type‐I photodynamic agents. As a proof of concept, BODIPY‐based photosensitizers were rationally designed and prepared. The photo‐induced intermolecular electron transfer between homotypic chromophores leads to the disproportionation reaction, resulting in the formation of charged intermediates, cationic and anionic radicals. The cationic radicals efficiently oxidize the cellularimportant coenzyme, tetrahydrobiopterin (BH4), and the anionic radicals transfer electrons to oxygen to produce superoxide radicals (O2−⋅). One of our Type‐I photodynamic agents not only self‐assembles in water but also effectively targets the endoplasmic reticulum. It displayed excellent photocytotoxicity even in highly hypoxic environments (2 % O2), with a half‐maximal inhibitory concentration (IC50) of 0.96 μM, and demonstrated outstanding antitumor efficacy in murine models bearing HeLa tumors. [ABSTRACT FROM AUTHOR]

The phototoxicity of photosensitizers (PSs) pre and post photodynamic therapy (PDT), and the hypoxic tumor microenvironment are two major problems limiting the application of PDT. While activatable PSs can successfully address the PS phototoxicity pre PDT, and type I PS can generate reactive oxygen species (ROS) effectively in hypoxic environment, very limited approaches are available for addressing the phototoxicity post PDT. There is virtually no solution available to address all these issues using a single design. Herein, we propose a proof‐of‐concept on‐demand switchable photosensitizer with quenched photosensitization pre and post PDT, which could be activated only in tumor hypoxic environment. Particularly, a hypoxia‐normoxia cycling responsive type I PS TPFN‐AzoCF3 was designed to demonstrate the concept, which was further formulated into TPFN‐AzoCF3 nanoparticles (NPs) using DSPE‐PEG‐2000 as the encapsulation matrix. The NPs could be activated only in hypoxic tumors to generate type I ROS during PDT treatment, but remain non‐toxic in normal tissues, pre or after PDT, thus minimizing side effects and improving the therapeutic effect. With promising results in in vitro and in vivo tumor treatment, this presented strategy will pave the way for the design of more on‐demand switchable photosensitizers with minimized side effects in the future. [ABSTRACT FROM AUTHOR]

The nucleus is considered the ideal target for anti‐tumor therapy because DNA and some enzymes in the nucleus are the main causes of cell canceration and malignant proliferation. However, nuclear target drugs with good biosafety and high efficiency in cancer treatment are rare. Herein, a nuclear‐targeted material MeTPAE with aggregation‐induced emission (AIE) characteristics was developed based on a triphenylamine structure skeleton. MeTPAE can not only interact with histone deacetylases (HDACs) to inhibit cell proliferation but also damage telomere and nucleic acids precisely through photodynamic treatment (PDT). The cocktail strategy of MeTPAE caused obvious cell cycle arrest and showed excellent PDT anti‐tumor activity, which offered new opportunities for the effective treatment of malignant tumors. [ABSTRACT FROM AUTHOR]

An ideal cancer treatment should not only destroy primary tumors but also improve the immunogenicity of the tumor microenvironment to achieve a satisfactory anti‐tumor immune effect. We designed a carbonic anhydrase IX (CAIX)‐anchored rhenium(I) photosensitizer, named CA‐Re, that not only performs type‐I and type‐II photodynamic therapy (PDT) with high efficiency under hypoxia (nanomolar‐level phototoxicity), but also evokes gasdermin D (GSDMD) mediated pyroptotic cell death to effectively stimulate tumor immunogenicity. CA‐Re could disrupt and self‐report the loss of membrane integrity simultaneously. This promoted the maturation and antigen‐presenting ability of dendritic cells (DCs), and fully activated T cells dependent adaptive immune response in vivo, eventually eliminating distant tumors at the same time as destroying primary tumors. To the best of our knowledge, CA‐Re is the first metal complex‐based pyroptosis inducer. [ABSTRACT FROM AUTHOR]

Keywords: anti-tumor immunity; carbonic anhydrase IX targeting; metallodrugs; photodynamic therapy; pyroptosis EN anti-tumor immunity carbonic anhydrase IX targeting metallodrugs photodynamic therapy pyroptosis 1 1 1 02/09/22 20220214 NES 220214 B Pyroptose b ist eine einzigartige Form des programmierten Zelltods, die im Wesentlichen proinflammatorisch und entscheidend für die Immunität ist. Anti-tumor immunity, carbonic anhydrase IX targeting, metallodrugs, photodynamic therapy, pyroptosis Innenrücktitelbild: A Carbonic Anhydrase IX (CAIX)-Anchored Rhenium(I) Photosensitizer Evokes Pyroptosis for Enhanced Anti-Tumor Immunity (Angew. [Extracted from the article]