Metalloimmunotherapy with Rhodium and Ruthenium Complexes: Targeting Tumor‐Associated Macrophages. Issue 24 (24th March 2022)

• Record Type: Journal Article
• Authors: Toupin, Nicholas; Herroon, Mackenzie K.; Thummel, Randolph P.; Turro, Claudia; Podgorski, Izabela; Gibson, Heather; Kodanko, Jeremy J.
• Is Part Of: Chemistry. Volume 28:Issue 24(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-24
• Subjects: antitumor agents -- immunotherapy -- macrophage -- rhodium -- ruthenium -- transition metals; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202104430
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Tumor associated macrophages (TAMs) suppress the cancer immune response and are a key target for immunotherapy. The effects of ruthenium and rhodium complexes on TAMs have not been well characterized. To address this gap in the field, a panel of 22 dirhodium and ruthenium complexes were screened against three subtypes of macrophages, triple‐negative breast cancer and normal breast tissue cells. Experiments were carried out in 2D and biomimetic 3D co‐culture experiments with and without irradiation with blue light. Leads were identified with cell‐type‐specific toxicity toward macrophage subtypes, cancer cells, or both. Experiments with 3D spheroids revealed complexes that sensitized the tumor models to the chemotherapeutic doxorubicin. Cell surface exposure of calreticulin, a known facilitator of immunogenic cell death (ICD), was increased upon treatment, along with a concomitant reduction in the M2‐subtype classifier arginase. Our findings lay a strong foundation for the future development of ruthenium‐ and rhodium‐based chemotherapies targeting TAMs. Abstract : Rhodium and ruthenium complexes are revealed as promising new agents for metalloimmunotherapy. Leads were identified that kill immunosuppressive M2 macrophages selectively, sensitize macrophage/cancer cell 3D co‐culture spheroids to a chemotherapeutic drug and increase cell surface exposure of calreticulin, a key event in immunogenic cell death.