Journal ArticleDOI
Ferroptosis‐Enhanced Cancer Immunity by a Ferrocene‐Appended Iridium(III) Diphosphine Complex
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TLDR
In this article , the IrIII complex (Ir1) containing a ferrocene-modified diphosphine ligand that localizes in lysosomes can effectively catalyze Fenton-like reaction, produce hydroxyl radicals, induce lipid peroxidation, down-regulate glutathione peroxidase 4 and result in ferroptosis.Abstract:
Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis-inducing agents have great potential as new antitumor candidates. Here, we report a IrIII complex (Ir1) containing a ferrocene-modified diphosphine ligand that localizes in lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton-like reaction, produce hydroxyl radicals, induce lipid peroxidation, down-regulate glutathione peroxidase 4, and result in ferroptosis. RNA sequencing analysis shows that Ir1 can significantly affect pathways related to ferroptosis and cancer immunity. Accordingly, Ir1 can induce immunogenic cells death and suppress tumor growth in vitro, regulate T cell activity and immune microenvironments in vivo. In conclusion, we show the potential of small molecules with ferroptosis-inducing capabilities for effective cancer immunotherapy. read more
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Journal ArticleDOI
Overcoming Hypoxia-Induced Ferroptosis Resistance via 19F/1H-MRI Traceable Core-Shell Nanostructure.
Zhe Dong,Peng Liang,Guoqiang Guan,Baoli Yin,Youjuan Wang,Renye Yue,Xiaobing Zhang,Guosheng Song +7 more
TL;DR: A novel kind of perfluorocarbon @ manganese oxide core-shell nanoparticles (PM-CS NPs) synthesized, which exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O2-mediated enhancement of key pathways of ferroPTosis.
Journal ArticleDOI
Simultaneous Photoactivation of cGAS-STING Pathway and Pyroptosis by Pt(II)-Triphenylamine Complexes for Cancer Immunotherapy.
Yuyi Ling,Xiao-Yu Xia,Liang Hao,Wen Jin Wang,Hong Zhang,Liu-Yi Liu,Wenting Liu,Zhiyun Li,Cai Ping Tan,Zong-Wan Mao +9 more
TL;DR: Overall, this work presents the first photoactivator of the cGAS-STING pathway, which may provide an innovative design strategy for anticancer immunotherapy.
Journal ArticleDOI
Perylene‐Mediated Electron Leakage in Respiratory Chain to Trigger Endogenous ROS Burst for Hypoxic Cancer Chemo‐Immunotherapy
TL;DR: In this article , the minimum lowest unoccupied molecular orbital (LUMO) energy level makes PDIC•NI most easily accept electrons from the oxidative respiratory chain to form lots of anions, and the resultant maximum ROS generation, establishing an unambiguous mechanism for the formation of perylene radical anions in the cell.
Journal ArticleDOI
Immunogenic Cell Death Inducing Metal Complexes for Cancer Therapy.
TL;DR: In this paper , the application of metal complexes as immunogenic cell death inducing compounds is systematically reviewed, and preliminary studies have shown that immunogenic cells death inducing agents could be able to overcome metastatic and relapsing tumors.
Journal ArticleDOI
Self-Amplifying Iridium(III) Photosensitizer for Ferroptosis-Mediated Immunotherapy Against Transferrin Receptor-Overexpressing Cancer.
Yuyi Ling,Wen Jin Wang,Liang Hao,Xiao-Wen Wu,Jing-Hao Liang,Hong Zhang,Zong-Wan Mao,Cai Ping Tan +7 more
TL;DR: In this paper , a small molecule-based photosensitizer with enhanced cancer immunotherapeutic properties by eliciting ferroptosis through a self-amplifying process was presented.
References
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Journal ArticleDOI
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Scott J. Dixon,Kathryn M. Lemberg,Michael R. Lamprecht,Rachid Skouta,Eleina M. Zaitsev,Caroline E Gleason,Darpan N Patel,Andras J. Bauer,Alexandra M. Cantley,Wan Seok Yang,Barclay Morrison,Brent R. Stockwell,Brent R. Stockwell +12 more
TL;DR: This paper identified the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes.
Journal ArticleDOI
Regulation of Ferroptotic Cancer Cell Death by GPX4
Wan Seok Yang,Rohitha SriRamaratnam,Matthew Welsch,Kenichi Shimada,Rachid Skouta,Vasanthi S. Viswanathan,Vasanthi S. Viswanathan,Jaime H. Cheah,Paul A. Clemons,Alykhan F. Shamji,Clary B. Clish,Lewis M. Brown,Albert W. Girotti,Virginia W. Cornish,Stuart L. Schreiber,Brent R. Stockwell +15 more
TL;DR: Targeted metabolomic profiling and chemoproteomics revealed that GPX4 is an essential regulator of ferroptotic cancer cell death and sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPx4-regulated ferroPTosis.
Journal ArticleDOI
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.
Sanjeev Mariathasan,Shannon J. Turley,Dorothee Nickles,Alessandra Castiglioni,Kobe C. Yuen,Yulei Wang,Edward E. Kadel,Hartmut Koeppen,Jillian L. Astarita,Rafael Cubas,Suchit Jhunjhunwala,Romain Banchereau,Yagai Yang,Yinghui Guan,Cecile Chalouni,James Ziai,Yasin Senbabaoglu,Stephen Santoro,Daniel Sheinson,Jeffrey Hung,Jennifer M. Giltnane,Andrew A. Pierce,Kathryn Mesh,Steve Lianoglou,Johannes Riegler,Richard A.D. Carano,Pontus Eriksson,Mattias Höglund,Loan Somarriba,Daniel L. Halligan,Michiel S. van der Heijden,Yohann Loriot,Jonathan E. Rosenberg,Lawrence Fong,Ira Mellman,Daniel S. Chen,Marjorie C. Green,Christina Louise Derleth,Gregg Fine,Priti S. Hegde,Richard Bourgon,Thomas Powles +41 more
TL;DR: Tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent were examined and major determinants of clinical outcome were identified and suggested that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.
Journal ArticleDOI
Ferroptosis as a p53-mediated activity during tumour suppression
TL;DR: It is shown that p53 inhibits cystine uptake and sensitizes cells to ferroptosis, a non-apoptotic form of cell death, by repressing expression of SLC7A11, a key component of the Cystine/glutamate antiporter.
Journal ArticleDOI
ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
Sebastian Doll,Bettina Proneth,Yulia Y. Tyurina,Elena Panzilius,Sho Kobayashi,Irina Ingold,Martin Irmler,Johannes Beckers,Michaela Aichler,Axel Walch,Holger Prokisch,Dietrich Trümbach,Gaowei Mao,Feng Qu,Hülya Bayır,Joachim Füllekrug,Christina Scheel,Wolfgang Wurst,Joel A. Schick,Valerian E. Kagan,José Pedro Friedmann Angeli,Marcus Conrad +21 more
TL;DR: Pharmacological targeting of ACSL4 with thiazolidinediones, a class of antidiabetic compound, ameliorated tissue demise in a mouse model of ferroptosis, suggesting that ACSL 4 inhibition is a viable therapeutic approach to preventing ferroPTosis-related diseases.
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