Photocatalytic Superoxide Radical Generator that Induces Pyroptosis in Cancer Cells

Le Yu, Yunjie Xu, Zhongji Pu, Heemin Kang, Mingle Li, Jonathan L. Sessler, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)


Pyroptosis, a newly characterized form of immunogenic cell death, is attracting increasing attention as a promising approach to cancer immunotherapy. However, biocompatible strategies to activate pyroptosis remain rare. Here, we show that a photocatalytic superoxide radical (O2-•) generator, NI-TA, triggers pyroptosis in cancer cells. NI-TA was designed to take advantage of an intramolecular triplet-ground state splitting energy modulation approach. Detailed studies revealed that the pyroptosis triggered by NI-TA under conditions of photoexcitation proceeds through a caspase-3/gasdermin E (GSDME) pathway rather than via canonical processes involving caspase-1/gasdermin-D (GSDMD). NI-TA was found to function via a partial-O2-recycling mode of action and to trigger cell pyroptosis and provide for effective cancer cell ablation even under conditions of hypoxia (≤2% O2). In the case of T47D 3D multicellular spheroids, good antitumor efficiency and stemness inhibition are achieved. This work highlights how photocatalytic chemistry may be leveraged to develop effective pyroptosis-inducing agents.

Original languageEnglish
Pages (from-to)11326-11337
Number of pages12
JournalJournal of the American Chemical Society
Issue number25
Publication statusPublished - 2022 Jun 29

Bibliographical note

Funding Information:
The authors gratefully acknowledge financial support received from the National Research Foundation of Korea (CRI Project Nos. 2018R1A3B1052702 and 2019M3E5D1A01068998, J.S.K.) and the Brain Pool Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (Grant No. 2020H1D3A1A02080172, M.L.). Support from the Robert A. Welch Foundation is also gratefully acknowledged (F-0018, J.L.S.). L.Y. thanks the China Scholarship Council (CSC, No. 2021907030009).

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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