An ER‐Targeting Iridium(III) Complex That Induces Immunogenic Cell Death in Non‐Small‐Cell Lung Cancer

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  • Lili Wang
    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510275 P. R. China
  • Ruilin Guan
    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510275 P. R. China
  • Lina Xie
    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510275 P. R. China
  • Xinxing Liao
    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510275 P. R. China
  • Kai Xiong
    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510275 P. R. China
  • Thomas W. Rees
    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510275 P. R. China
  • Yu Chen
    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510275 P. R. China
  • Liangnian Ji
    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510275 P. R. China
  • Hui Chao
    MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of Chemistry Sun Yat-Sen University Guangzhou 510275 P. R. China

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<jats:title>Abstract</jats:title><jats:p>Immunogenic cell death (ICD) is a vital component of therapeutically induced anti‐tumor immunity. An iridium(III) complex (<jats:bold>Ir1</jats:bold>), containing an<jats:italic>N</jats:italic>,<jats:italic>N</jats:italic>‐bis(2‐chloroethyl)‐azane derivate, as an endoplasmic reticulum‐localized ICD inducer for non‐small cell lung cancer (NSCLC) is reported. The characteristic discharge of damage‐associated molecular patterns (DAMPs), that is, cell surface exposure of calreticulin (CRT), extracellular exclusion of high mobility group box 1 (HMGB1), and ATP, were generated by<jats:bold>Ir1</jats:bold>in A549 lung cancer cells, accompanied by an increase in endoplasmic reticulum stress and reactive oxygen species (ROS). The vaccination of immunocompetent mice with<jats:bold>Ir1</jats:bold>‐treated dying cells elicited an antitumor CD8<jats:sup>+</jats:sup>T cell response and Foxp3<jats:sup>+</jats:sup>T cell depletion, which eventually resulted in long‐acting anti‐tumor immunity by the activation of ICD in lung cancer cells.<jats:bold>Ir1</jats:bold>is the first Ir‐based complex that is capable of developing an immunomodulatory response by immunogenic cell death.</jats:p>

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