Volume 137, Issue 30 e202507157
Forschungsartikel

Nonconjugated Structural Distortion Promoting the Formation of NIR Triplet States in Phenothiazine Dyes for Cancer Photoimmunotherapy

Xiang Xia

Xiang Xia

Ningbo Institute of Dalian University of Technology, 26 Yucai Road, Jiangbei District, Ningbo, 315016 China

State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024 China

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Ran Wang

Ran Wang

State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024 China

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Yingqi Hu

Yingqi Hu

State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024 China

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Saran Long

Saran Long

State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024 China

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Wen Sun

Corresponding Author

Wen Sun

Ningbo Institute of Dalian University of Technology, 26 Yucai Road, Jiangbei District, Ningbo, 315016 China

State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024 China

E-mail: [email protected]; [email protected]

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Jiangli Fan

Corresponding Author

Jiangli Fan

Ningbo Institute of Dalian University of Technology, 26 Yucai Road, Jiangbei District, Ningbo, 315016 China

State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024 China

E-mail: [email protected]; [email protected]

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Xiaojun Peng

Xiaojun Peng

State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024 China

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First published: 19 May 2025

Abstract

Near-infrared (NIR) triplet-state dyes are pivotal for advanced biomedical and material science applications. Although numerous strategies have been proposed to enhance the photosensitization efficiency of dyes, significant challenges remain. Herein, we propose a novel strategy leveraging nonconjugated structural distortion to enhance triplet-state formation. This strategy, achieved by introducing steric groups at the edges of the phenothiazine (PTZ) dye framework, notably enhances intersystem crossing (ISC) and prolongs triplet-state lifetime. Based on this strategy, HNBS and HNBSe are synthesized, which exhibit exceptional triplet-state quantum yields (47.2% for HNBS and 87.7% for HNBSe) and prolonged triplet-excited-state lifetimes (21.1 µs for HNBS and 6.3 µs for HNBSe). These values substantially exceed those of conventional dyes, such as NBS (negligible and NBSe (3.2 µs). Under ultralow-light doses (0.45 J cm2 in vitro, and 6 J cm2 in vivo), these photosensitizers demonstrate robust tumor cell inhibition, highlighting their exceptional photosensitizing ability. Mechanistically, HNBS possesses lysosomal-targeting ability, and upon light irradiation, it induces lysosomal damage, triggering pyroptosis and immunogenic cell death. These processes promote dendritic cell maturation and T-cell differentiation, augmenting the immune response and enabling effective photoimmunotherapy.

Conflict of Interests

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available in Supporting Information of this article.

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