Citation: Shi-Hao Wang, Qiu-Yi Duan, Rufeng Zhang, Zihao Wang, Zi-Xi Wang, Yang Shen, Fu-Gen Wu. A liquid PEG depot capable of triggering intratumoral O₂/H₂O₂ generation and neutralization/calcification for realizing light irradiation-free photodynamic therapy and immunotherapy[J]. Chinese Chemical Letters, ;2026, 37(8): 111772. doi: 10.1016/j.cclet.2025.111772 shu

A liquid PEG depot capable of triggering intratumoral O₂/H₂O₂ generation and neutralization/calcification for realizing light irradiation-free photodynamic therapy and immunotherapy

Shi-Hao Wang ^a ,
Qiu-Yi Duan ^a ,
Rufeng Zhang ^a ,
Zihao Wang ^a ,
Zi-Xi Wang ^a ,
Yang Shen ^{b, c, *,} ,
Fu-Gen Wu ^{a, b, c, d, e, *,}

a.
State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 211189, China
b.
Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
c.
Nanjing Key Laboratory of Intelligent Obstetrics and Gynecology Medicine, Nanjing 210009, China
d.
Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning 530021, China
e.
Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning 530021, China

shenyang@seu.edu.cn

wufg@seu.edu.cn

Received Date: 30 May 2025
Revised Date: 27 August 2025
Accepted Date: 28 August 2025
Available Online: 29 August 2025

Figures(4)

The clinical application of photodynamic therapy (PDT) is usually limited by the low penetration depth of light and the hypoxic condition of tumor microenvironment. Therefore, it is urgent to develop a drug system that can activate photosensitizers (PSs) in deeply seated tumors and spontaneously generate O₂ to enhance the efficacy of PDT. Herein, we design a liquid polyethylene glycol (PEG) 200 (PEG₂₀₀)-based drug depot containing calcium peroxide (CaO₂) nanoparticles, bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl]oxalate (CPPO, a high-energy compound), and chlorin e6 (Ce6, a PS) for achieving O₂/H₂O₂ self-supplied chemiexcited (light irradiation-free) PDT and immunotherapy. By injecting the drug depot into the tumor, CaO₂ can react with water to produce H₂O₂, which can activate CPPO to generate chemical energy, further stimulating Ce6 to produce ¹O₂. Meanwhile, CaO₂ can also generate O₂ to enhance PDT. Besides, CaO₂ can neutralize the acidic tumor microenvironment by the formation of Ca(OH)₂, cause calcium overload in tumor cells, and lead to tumor calcification. Further experiments show that CaO₂, CPPO, and Ce6 can cause mitochondrial damage, trigger immunogenic cell death, and significantly improve the therapeutic effect of programmed death-1 (PD-1) monoclonal antibody. This work highlights the application potential of the rational combination of CaO₂, CPPO, and Ce6 for realizing light irradiation-free PDT and immunotherapy.
- Chemiexcited photodynamic therapy,
- Calcium peroxide,
- Immunogenic cell death,
- Calcium overload,
- Immunotherapy
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A liquid PEG depot capable of triggering intratumoral O2/H2O2 generation and neutralization/calcification for realizing light irradiation-free photodynamic therapy and immunotherapy

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通讯作者: 陈斌, bchen63@163.com

A liquid PEG depot capable of triggering intratumoral O₂/H₂O₂ generation and neutralization/calcification for realizing light irradiation-free photodynamic therapy and immunotherapy