TY - JOUR
T1 - Photocatalytic Superoxide Radical Generator that Induces Pyroptosis in Cancer Cells
AU - Yu, Le
AU - Xu, Yunjie
AU - Pu, Zhongji
AU - Kang, Heemin
AU - Li, Mingle
AU - Sessler, Jonathan L.
AU - Kim, Jong Seung
N1 - 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.
PY - 2022/6/29
Y1 - 2022/6/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85133144166&partnerID=8YFLogxK
U2 - 10.1021/jacs.2c03256
DO - 10.1021/jacs.2c03256
M3 - Article
C2 - 35708298
AN - SCOPUS:85133144166
SN - 0002-7863
VL - 144
SP - 11326
EP - 11337
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 25
ER -
