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Endoplasmic Reticulum-Targeting NIR Cyanine ER800 Nanoparticles Promote Pyroptosis in Triple-Negative Breast Cancer
Jiawang Yang1, Jijun Jiang1, Yuanzhi Yang1
1Key Laboratory of Basic Pharmacology of Ministry of Education, Chinese Pharmacological Society-Guizhou Province Joint Laboratory for Pharmacology, Zunyi Medical University, Zunyi, Guizhou 563000, China.
ACS Applied Materials & Interfaces
|May 15, 2026
Summary
Researchers developed novel ER800-FA-NPs for targeting endoplasmic reticulum stress and inducing pyroptosis in triple-negative breast cancer. This theranostic approach integrates imaging and therapy, showing promising antitumor effects in preclinical models.
Area of Science:
- Oncology
- Cell Biology
- Nanomedicine
Background:
- Pyroptosis, an inflammatory cell death, is a promising anticancer strategy.
- Endoplasmic reticulum (ER)-targeted pyroptosis offers theranostic potential by combining imaging and therapy.
- Development of ER-targeting theranostic agents for pyroptosis induction is an unmet need.
Purpose of the Study:
- To develop an ER-targeting theranostic agent for integrated tumor imaging and cancer therapy.
- To investigate the efficacy of ER800-FA-NPs in triggering pyroptosis and treating triple-negative breast cancer (TNBC).
Main Methods:
- Synthesis of ER-targeting NIR fluorescent cyanine ER800 and construction of ER800-FA-NPs.
- In vitro assessment of ER targeting and pyroptosis in TNBC cells using flow cytometry, immunofluorescence, and Western blotting.
- In vivo evaluation of antitumor efficacy in a TNBC xenograft model.
Main Results:
- ER800-FA-NPs selectively accumulated in the ER of TNBC cells, inducing ER stress via ROS generation.
- Activated ER stress pathways (GRP78, PERK, ATF6, IRE1) led to pyroptosis markers (LDH, IL-1β, IL-18, caspase-3/GSDME cleavage).
- In vivo studies demonstrated significant tumor targeting and antitumor effects in TNBC models.
Conclusions:
- ER800-FA-NPs effectively induce pyroptosis through the caspase-3/GSDME pathway in TNBC.
- These NPs show potential as theranostic agents for imaging-guided therapy in TNBC.
- ER-targeted pyroptosis represents a viable strategy for TNBC treatment.
