Naphthalimide‐Based Type‐I Nano‐Photosensitizers for Enhanced Antitumor Photodynamic Therapy: H <sub>2</sub> S Synergistically Regulates PeT and Self‐Assembly

H Huiyu Niu (Key Laboratory of Green Chemical Media and Reactions Ministry of Education Henan International Joint Laboratory of Smart Molecules and Identification and Diagnostic Functions Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals School of Chemistry and Chemical Engineering Henan Normal University Xinxiang Henan 453007 P.R. China) S Songnan Wang (Key Laboratory of Green Chemical Media and Reactions Ministry of Education Henan International Joint Laboratory of Smart Molecules and Identification and Diagnostic Functions Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals School of Chemistry and Chemical Engineering Henan Normal University Xinxiang Henan 453007 P.R. China) Y Yang Liu N Nana Ma (Henan Key Laboratory of Boron Chemistry and Advanced Energy Materials Key Laboratory of Green Chemical Media and Reactions Ministry of Education, School of Chemistry and Chemical Engineering Henan Normal University Xinxiang China) S Shuaiwei Cheng (Key Laboratory of Green Chemical Media and Reactions Ministry of Education Henan International Joint Laboratory of Smart Molecules and Identification and Diagnostic Functions Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals School of Chemistry and Chemical Engineering Henan Normal University Xinxiang Henan 453007 P.R. China) B Beidou Feng (Collaborative Innovation Centre of Henan Province For Green Manufacturing of Fine Chemicals Key Laboratory of Green Chemical Media and Reactions Ministry of Education, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation School of Chemistry and Chemical Engineering Henan Normal University Xinxiang China) H Hyunsun Jeong (Department of Chemistry and Nanoscience) Y Yonggang Yang (State Key Laboratory of Quantum Optics Technologies and Devices, Institute of Laser Spectroscopy, Shanxi University 1 , Taiyuan 030006,) G Ge Wang T Tony D. James (University of Bath , , ,) J Juyoung Yoon (Department of Chemistry and Nanoscience) J Jonathan L. Sessler H Hua Zhang

Abstract

Abstract Photodynamic therapy (PDT) relies on a combination of light and photosensitizers (PSs) to achieve local control over cancerous lesions. However, it is subject to limitations, including tumor hypoxia, low tumor targeting, off‐target phototoxicity, and always‐on fluorescence. Here, we propose a design strategy for activated nano‐PSs (N‐PSs) to simultaneously overcome the limitations of PDT, wherein photoinduced electron transfer (PeT) is coupled with an endogenous H 2 S‐regulated self‐association process to promote Type‐I photochemical reactions. Using theoretical calculations, spectral analysis, and microscopic imaging, we verified the generation of self‐assembly and occurrence of PeT. And it was also shown that H 2 S could synergistically inhibit the PeT and self‐assembly, reflecting by a 21‐fold increase in fluorescence intensity at 635 nm and 35‐fold enhancement of the Type‐I photochemical reaction as inferred from O 2 − generation. Moreover, the most promising self‐assembled N‐PS, Ts3‐ONB , was found to almost completely inhibit tumor growth in mice under two‐photon excitation through the synergistic regulation of PeT and self‐assembly by endogenous H 2 S ( V 14 days Ts3‐ONB + Light group / V 14 days Control group  ≈ 0.02). As such, the synergistic combination of PeT and self‐assembly is an effective design strategy for developing advanced N‐PSs that can address some current PDT limitations.

Article Details

Volume / Issue Vol. 64, Issue 48
Published November 24, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (13)

H

Huiyu Niu

Key Laboratory of Green Chemical Media and Reactions Ministry of Education Henan International Joint Laboratory of Smart Molecules and Identification and Diagnostic Functions Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals School of Chemistry and Chemical Engineering Henan Normal University Xinxiang Henan 453007 P.R. China

S

Songnan Wang

Key Laboratory of Green Chemical Media and Reactions Ministry of Education Henan International Joint Laboratory of Smart Molecules and Identification and Diagnostic Functions Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals School of Chemistry and Chemical Engineering Henan Normal University Xinxiang Henan 453007 P.R. China

Y

Yang Liu

N

Nana Ma

Henan Key Laboratory of Boron Chemistry and Advanced Energy Materials Key Laboratory of Green Chemical Media and Reactions Ministry of Education, School of Chemistry and Chemical Engineering Henan Normal University Xinxiang China

S

Shuaiwei Cheng

Key Laboratory of Green Chemical Media and Reactions Ministry of Education Henan International Joint Laboratory of Smart Molecules and Identification and Diagnostic Functions Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals School of Chemistry and Chemical Engineering Henan Normal University Xinxiang Henan 453007 P.R. China

B

Beidou Feng

Collaborative Innovation Centre of Henan Province For Green Manufacturing of Fine Chemicals Key Laboratory of Green Chemical Media and Reactions Ministry of Education, Henan Key Laboratory of Organic Functional Molecule and Drug Innovation School of Chemistry and Chemical Engineering Henan Normal University Xinxiang China

H

Hyunsun Jeong

Department of Chemistry and Nanoscience

Y

Yonggang Yang

State Key Laboratory of Quantum Optics Technologies and Devices, Institute of Laser Spectroscopy, Shanxi University 1 , Taiyuan 030006,

G

Ge Wang

T

Tony D. James

University of Bath , , ,

J

Juyoung Yoon

Department of Chemistry and Nanoscience

J

Jonathan L. Sessler

H

Hua Zhang