Endoplasmic Reticulum-Targeting NIR Cyanine ER800 Nanoparticles Promote Pyroptosis in Triple-Negative Breast Cancer.

Authors

Jiawang Yang, Jijun Jiang, Yuanzhi Yang, Zhilin Shen, Zhixuan Lin, Xianpin Gao, Wei Wu, Zongjian Ye, Jie Gao, Ning Gao

Published in

ACS applied materials & interfaces. Volume 18. Issue 20. Pages 28423-28438. May 27, 2026. Epub May 15, 2026.

Abstract

Pyroptosis, an inflammatory form of cell death, has recently attracted increasing attention in anticancer therapy. Endoplasmic reticulum (ER)-targeted pyroptosis has emerged as a highly promising strategy in theranostics, integrating tumor imaging and therapeutic interventions. Research on the use of ER-targeted theranostic agents for triggering pyroptosis is lacking. This study aims to develop an ER-targeting theranostic agent that enables the integration of tumor imaging and cancer-targeted therapeutics. The ER-targeting NIR fluorescent cyanine ER800 was synthesized, and ER800-FA-NPs were constructed. Flow cytometry, immunofluorescence, and Western blotting were employed to assess the ER targeting effect and pyroptosis in triple-negative breast cancer (TNBC) cells in vitro. A TNBC cell xenograft model was used to investigate the antitumor efficacy. ER800-FA-NPs preferentially accumulate in the ER of TNBC cells, subsequently promoting ER stress via the generation of ROS. High ER stress triggers the activation of the GRP78-mediated PERK-eIF2α-ATF4-CHOP, ATF6, and IRE1-XBP1 signaling pathways, leading to LDH, IL-1β, and IL-18 release and cleavage of caspase-3/GSDME and ultimately promoting pyroptosis. In vivo experiments revealed that ER800-FA-NPs exhibited excellent tumor-targeting ability and antitumor efficacy against TNBC through caspase-3/GSDME pathway-mediated pyroptosis. Our research findings indicate that ER800-FA-NPs may serve as theranostic agents in tumor imaging-guided therapy, further supporting the use of ER-targeted pyroptosis for the treatment of TNBC.

PMID:
42138395
Bibliographic data and abstract were imported from PubMed on 17 Sep 2026.

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