Citation: Xinyu Wang, Yunquan Yang, Shaojing Zhao, Yuanyu Tang, E Pang, Wenjie Gao, Jiwei Li, Qingxu Diao, Lianhong Zou, Jie Zeng, Minhuan Lan, Jianing Yi. Synergistic antitumor therapy via immunophototherapy induced multi-modal cell death and immune microenvironment reprogramming[J]. Chinese Chemical Letters, ;2026, 37(10): 112129. doi: 10.1016/j.cclet.2025.112129 shu

Synergistic antitumor therapy via immunophototherapy induced multi-modal cell death and immune microenvironment reprogramming

Xinyu Wang ^a ,
Yunquan Yang ^a ,
Shaojing Zhao ^b ,
Yuanyu Tang ^b ,
E Pang ^b ,
Wenjie Gao ^c ,
Jiwei Li ^d ,
Qingxu Diao ^e ,
Lianhong Zou ^{e, *,} ,
Jie Zeng ^{f, *,} ,
Minhuan Lan ^{b, *,} ,
Jianing Yi ^{e, f, *,}

a.
Department of General Surgery, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha 410005, China
b.
College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China
c.
Department of General Surgery, Sir Run Run Hospital of Nanjing Medical University, Nanjing 211166, China
d.
Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha 410000, China
e.
Institute of Clinical and Translational Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, China
f.
Department of Breast and Thyroid Gland Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, China

yijianing@hunnu.edu.cn

minhuanlan@csu.edu.cn

zengjie227@hunnu.edu.cn

zoulh1986@hunnu.edu.cn

Received Date: 20 July 2025
Revised Date: 16 November 2025
Accepted Date: 17 November 2025
Available Online: 17 November 2025

Figures(7)

This study aims to develop advanced phototheranostic agent to address the critical challenge of multi-modal therapy and immune microenvironment remodeling in immuno-phototherapy (IPT). Here we utilized a near infrared (NIR) o-IDTBR, and then assembled with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)] (DSPE-PEG-NH₂) to prepare o-IDTBR nanoparticles (NPs). Theoretical calculations suggest that in the aggregated state, the energy gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), and the energy gap between the excited singlet and triplet states are reduced, as compared to the monomolecular state, leading to red-shifting absorption/emission wavelengths and enhancing the photothermal conversion and reactive oxygen species (ROS) generation, and thus improve the efficacy of photodynamic and photothermal therapies. These NIR laser-activated NPs effectively induced pyroptosis/apoptosis/necroptosis (PANoptosis) and promoted immunogenic cell death through mechanisms such as calreticulin (CRT) exposure, ATP secretion, and high mobility group box 1 (HMGB1) release. Notably, immune profiling revealed a reprogrammed tumor microenvironment in NPs and laser irradiation treated group. This phenotypic shift activated systemic antitumor immunity. Our work constructs an advanced phototheranostic agent with aggregation-induced red-shifting absorption and fluorescence wavelengths, and enhancing photothermal conversion and ROS generation capabilities, and establishes a synergistic paradigm of "imaging guidance, inducing local multi-modal cell death, systemic immune activation".
- Aggregate,
- Near infrared,
- Immuno-phototherapy,
- Immunogenic cell death,
- PANoptosis
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