Photochemical and biological dual-effects enhance the inhibition of photosensitizers for tumour growth

Huiyu Niu, Yang Liu, Yafu Wang, Yonggang Yang, Ge Wang, Tony D. James, Jonathan L. Sessler, Hua Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Photosensitizers typically rely on a singular photochemical reaction to generate reactive oxygen species, which can then inhibit or eradicate lesions. However, photosensitizers often exhibit limited therapeutic efficiency due to their reliance on a single photochemical effect. Herein, we propose a new strategy that integrates the photochemical effect (type-I photochemical effect) with a biological effect (proton sponge effect). To test our strategy, we designed a series of photosensitizers (ZZ-sers) based on the naphthalimide molecule. ZZ-sers incorporate both a p-toluenesulfonyl moiety and weakly basic groups to activate the proton sponge effect while simultaneously strengthening the type-I photochemical effect, resulting in enhanced apoptosis and programmed cell death. Experiments confirmed near-complete eradication of the tumour burden after 14 days (Wlight/Wcontrol ≈ 0.18, W represents the tumour weight). These findings support the notion that the coupling of a type-I photochemical effect with a proton sponge effect can enhance the tumour inhibition by ZZ-sers, even if the basic molecular backbones of the photosensitizers exhibit nearly zero or minimal tumour inhibition ability. We anticipate that this strategy can be generalized to develop additional new photosensitizers with improved therapeutic efficacy while overcoming limitations associated with systems relying solely on single photochemical effects.

Original languageEnglish
JournalChemical Science
Early online date25 Apr 2024
DOIs
Publication statusE-pub ahead of print - 25 Apr 2024

Data Availability Statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or its ESI†].

ASJC Scopus subject areas

  • General Chemistry

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