Naphthalimide-Based Type-I Nano-Photosensitizers for Enhanced Antitumor Photodynamic Therapy: H2S Synergistically Regulates PeT and Self-Assembly

Authors

Huiyu Niu
Songnan Wang
Yang Liu
Nana Ma
Shuaiwei Cheng
Beidou Feng
Hyunsun Jeong
Yonggang Yang
Ge Wang
Tony D James
Juyoung Yoon
Jonathan L Sessler
Hua Zhang

Language

English

Publication Date

11-24-2025

Journal

Angewandte Chemie

DOI

10.1002/anie.202512150

PMID

41047818

PMCID

PMC12643349

PubMedCentral® Posted Date

10-6-2025

PubMedCentral® Full Text Version

Post-print

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 H2S‐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 H2S 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 O2 − 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 H2S (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.

Keywords

Photochemotherapy, Photosensitizing Agents, Animals, Mice, Hydrogen Sulfide, Humans, Antineoplastic Agents, Naphthalimides, Electron Transport, Nanoparticles, Cell Proliferation, Cell Line, Tumor, H2S, Naphthalimide, Photoinduced electron transfer, Self‐assembly, Type‐I photosensitizers

Published Open-Access

yes

Recommended Citation

Niu, Huiyu; Wang, Songnan; Liu, Yang; et al., "Naphthalimide-Based Type-I Nano-Photosensitizers for Enhanced Antitumor Photodynamic Therapy: H2S Synergistically Regulates PeT and Self-Assembly" (2025). Faculty, Staff and Student Publications. 6184.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6184