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journal article·2025-06Open access

A Mitochondrion‐Targeted NIR‐II Modulator for Synergistic Ferroptosis–Immunotherapy

Miao Wang, Qihang Ding, Wuyue Su, Min Luo, Runping Yang, Guopeng Chen, Qian Wang, Nan Zhang, Jialu Gao, Xiaofen Wang, Tianhe Huang, Pan Liu, Dujiang Fu, Xuechuan Hong, Xiaodong Zeng, Yongchang Wei, Yuling Xiao

Small· Volume 21· Issue 22
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Source abstract

Abstract

Abstract Immune checkpoint inhibitors (ICIs) have limited clinical efficacy against gastric cancer (GC) due to the nonimmunogenic tumor microenvironment. Therefore, inducing immunogenic cell death (ICD) to reprogram the immunogenic landscape is essential. This study develops HD‐FA nanoparticles by encapsulating a novel mitochondrion‐targeted NIR‐II modulator, HD, within DSPE‐PEG‐FA. HD‐FA exhibits superior spatiotemporal resolution, robust tumor accumulation, and minimal adverse effects. Upon 808 nm laser irradiation, HD‐FA generates reactive oxygen species, leading to ferroptosis and oxidative stress damage in GC cells by inhibiting the SLC7A11/GSH/GPX4 axis. HD‐FA triggers ICD, resulting in antitumor activity not only in primary tumors but also in distant tumors. Moreover, HD‐FA promotes dendritic cell maturation, increases the effector‐memory T‐cell frequency, and reduces the presence of myeloid‐derived suppressor cells, thereby fostering enhanced antitumor immunity. This study presents the first report of a novel NIR‐II modulator for GC immunogenic synergistic therapy with ICIs, marking significant advancements in the fight against GC.
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Research context

Nanomaterials

OpenAlex topics: Ferroptosis and cancer prognosis · Cancer Immunotherapy and Biomarkers · Nanoplatforms for cancer theranostics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University Hubei Cancer Clinical Study Center & Hubei Key Laboratory of Tumor Biological Behaviors School of Pharmaceutical Sciences Wuhan 430071 China

State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China

Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug Discovery Yantai 264117 China

Department of Chemistry Korea University Seoul 02841 South Korea

Shenzhen Institute of Wuhan University Shenzhen 518057 China

Department of Dermatology The Sixth Medical Center of Chinese PLA General Hospital Beijing 100048 China

Department of Hematology Zhongnan Hospital of Wuhan University Wuhan 430071 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Basic and Applied Basic Research Foundation of Guangdong Province · Natural Science Foundation of Shandong Province

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