Citation: Zekun Gao, Xiuli Zheng, Weimin Liu, Jie Sha, Shuaishuai Bian, Haohui Ren, Jiasheng Wu, Wenjun Zhang, Chun-Sing Lee, Pengfei Wang. GSH-activatable copper-elsinochrome off-on photosensitizer for combined specific NIR-Ⅱ two-photon photodynamic/chemodynamic therapy[J]. Chinese Chemical Letters, ;2025, 36(3): 109874. doi: 10.1016/j.cclet.2024.109874 shu

GSH-activatable copper-elsinochrome off-on photosensitizer for combined specific NIR-Ⅱ two-photon photodynamic/chemodynamic therapy

Zekun Gao ^{a, b} ,
Xiuli Zheng ^{a, *,} ,
Weimin Liu ^{a, b} ,
Jie Sha ^{a, b} ,
Shuaishuai Bian ^{a, b} ,
Haohui Ren ^a ,
Jiasheng Wu ^a ,
Wenjun Zhang ^c ,
Chun-Sing Lee ^c ,
Pengfei Wang ^{a, b, *,}

a.
Key Laboratory of Photochemical Conversion and Optoelectronic Materials and CityU-CAS Joint Laboratory of Functional Materials and Devices, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
b.
School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China
c.
Center of Super-Diamond and Advanced Films (COSDAF) & Department of Materials Science and Engineering, City University of Hong Kong, Hong Kong SAR 999077, China

zhengxiuli@mail.ipc.ac.cn

wangpf@mail.ipc.ac.cn

Received Date: 24 January 2024
Revised Date: 2 April 2024
Accepted Date: 8 April 2024
Available Online: 9 April 2024

Figures(6)

The complexity of cancer therapy has led to the emergence of combination therapy as a promising approach to enhance treatment efficacy and safety. The integration of glutathione (GSH)-activatable two-photon photodynamic therapy (TP-PDT) and chemodynamic therapy (CDT) offers the possibility to advance precision and efficacy in anti-cancer treatments. In this study, a GSH-activatable photosensitizer (PS), namely copper-elsinochrome (CuEC), is synthesized and utilized for combination second near-infrared (NIR-Ⅱ) TP-PDT/CDT. The Cu²⁺ acts as a “lock”, suppressing the fluorescence and ¹O₂ generation ability of EC in a normal physiological environment (“OFF” state). However, the overexpressed GSH in the tumor microenvironment acts as the “key”, resulting in the release of EC (“ON” state) and Cu⁺ (reduced by GSH). The released EC can be utilized for fluorescence imaging and TP-PDT under NIR-Ⅱ (λ = 1000 nm) two-photon excitation, while Cu⁺ can generate highly toxic hydroxyl radicals (^•OH) via Fenton-like reaction for CDT. Additionally, this process consumes GSH and diminishes the tumor’s antioxidant capacity, thereby augmenting the efficacy of combination therapy. The CuEC achieves significant tumor cell ablation in both 2D monolayer cells and 3D multicellular tumor spheres through the combination of NIR-Ⅱ TP-PDT and CDT.
- GSH activation,
- Copper-elsinochrome photosensitizer,
- Reactive oxygen species,
- NIR-Ⅱ two-photon photodynamic therapy,
- Chemodynamic therapy
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